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Stem Cell Research: Potentials Annual magazine of the GSCN & Perspectives 2016/17 genetic

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ISSN (Print) 2198-7831 ISSN (Online) 2198-784X

IMPRINT German Stem Cell Network e.V. Annual Magazine 2016/17 © 2017 GSCN Publisher German Stem Cell Network c/o Max Delbrück Center for Molecular Medicine (MDC) Robert-Rössle-Str. 10 13125 Berlin phone: +49 30 9406 24-87/-88 fax: +49 30 9406 2486 e-mail: [email protected] URL: www.gscn.org Editors Stefanie Mahler, Daniel Besser, Ulrike Papra (Central Office GSCN) Philipp Graf (BIOCOM AG) GSCN pictures were taken by Anna Junge and Stefanie Mahler Translation Marie Klein, Berlin Design & Layout unicom Werbeagentur GmbH Print Buch- und Offset-Druckerei H. Heenemann Circulation: 1.200 Copyright The magazine is part of the public relations work of the GSCN and funded by the German Federal Ministry of Education and Research (BMBF). It is supplied for a protective fee of 2€ (Including postage) and must not be resold. Reprint only with permission by the editors. Disclaimer: As with all writings of the GSCN the person designations in favor of a better reading fluency are always gender neutral. ISSN (Print) 2198-7831 ISSN (Online) 2198-784X

Stem Cell Research: Potentials & Perspectives

WELCOME NOTE THOMAS RACHEL

Welcome Note

I

t is exactly ten years ago that a trailblazing technology fundamentally changed our lives with the introduction of the smartphone. At the same time, a similar revolution also took place in the field of biomedical research: Scientists generated induced pluripotent stem cells (iPS cells) from mice and human beings. A further revolutionary technology – genome surgery using the CRISPR/Cas system – is just five years old.

These highly innovative biomedical technologies present entirely new approaches to researching diseases. Stem cells have become an essential instrument for basic biomedical research, for the development of drugs and for testing active substances. They also have potential for the development of new treatments for patients. German stem cell research is making an important contribution towards this effort. This is reflected not least in the great response to the recent call for proposals in the field of innovative stem cell technologies for individualized medicine issued by the Federal Ministry of Education and Research (BMBF). Over the next three years, the BMBF will provide funding of approximately 21 million euros for a total of 13 research collaborations nationwide with the aim of translating stem cell technologies into medical applications.

Annual GSCN Magazine 2016/17

The working groups which are now being funded are profiting from the existence of the German Stem Cell Network – GSCN. The BMBF has been funding the development of the GSCN since 2013 and the latter has quickly established itself as an important national forum. It serves as the contact point for international partners and industry as well as communicating with society at large. The GSCN’s annual conferences have become a central meeting place for the German stem cell research community.

This year’s GSCN magazine explores the potential and prospects of stem cell research in Germany, highlights career opportunities as well as ways to familiarize a wider public with the world of stem cells. Stem cell research is a key driver for innovation in the medicine of the future and I sincerely hope that the Network will continue to maintain and expand its commitment to science and industry.

Thomas Rachel MdB Parliamentary State Secretary to the Federal Minister of Education and Research

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Chromosomes of human fibroblasts with telomers stained in red

We

are the

GSCN 4


PREFACE K. LENHARD RUDOLPH

Preface

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ow in its fifth year, the German Stem Cell Network GSCN has worked tremendously hard and achieved a great deal over the last four years. Today, the GSCN plays an invaluable role in bringing together stem cell researchers from across the spectrum, connecting research projects and advising political decision-makers on issues relating to stem cell research. It is serving as a critical and expert guide in the public discourse on stem cell research and the opportunities it holds to develop new therapies in the future.

Research undertaken in the last few years has shown that stem cells are of fundamental significance in the development of disease in older age. We now know that 50 percent of 70-year-olds have mutated stem cell clones in their blood, which are a cause of cardiovascular diseases and cancer and reduce life expectancy in old age. Recent studies have shown that cell reprogramming of induced pluripotent stem cells (iPS cells) can be used to develop models to investigate the cause of diseases and test new therapies to mitigate their effects.

Photos: FLI, Rudolph Lab / Nadine Grimme / GSCN

In view of the rapidly increasing potential of stem cell research, the GSCN is becoming ever more important as a mediator of knowledge transfer, as a communication platform, as an advisor to policymakers and the general public, and as a catalyst in the development of stem cell research. At the same time, however, the funding for the GSCN from the Federal Ministry of Education and Research (BMBF) is coming to an end this year and the future financing of the GSCN has not yet been secured. The uncertain future of the GSCN is indicative of a general weakness in the German research system. Professional associations in Germany are usually financed through membership fees and by partners from industry. In new, emerging research fields like stem cell research, the funds generated from these sources are not sufficient for the professional association to fulfill its key role in develop-


ing the research area. One of our main tasks this year is therefore to consult with political representatives to find possible solutions that will enable the GSCN to continue its highly successful work and support the further development of stem cell research in Germany. A conceivable option, for example, would be a transitional financing scheme.

Let us therefore make a concerted effort in 2017 to ensure that the GSCN is able secure the funding it needs to continue its successful work in supporting the development of stem cell research and driving its potential for translational application.

I would like to invite you all most warmly to the next annual conference of the GSCN in September 2017 in Jena, where you will be able to gain an overview of the latest developments and opportunities in stem cell research. Our relatively young research field is undoubtedly one of the most dynamic areas in biomedicine. I look forward to further consolidating its position in Germany, to my work in the GSCN this year, and to leading this valuable network into a secure future. I hope that you find this latest issue of our annual magazine an interesting and inspiring read. Best regards

K. Lenhard Rudolph President

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INDEX

Welcome Note Thomas Rachel (BMBF)�� 3

11

8

Preface K. Lenhard Rudolph, acting GSCN President�� 5

“The GSCN is the largest network on stem cell research in Germany” Interview with K. Lenhard Rudolph�� 8

GSCN News from the Central Office�� 11 Novel trends and technologies in stem cell research 4th Annual Conference of the GSCN�� 16

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27

International comparision 27

A close look at public research funding

Research and application 33

33 6

The future of stem cell research

INDEX

Regenerative medicine 41

Testing clinical maturity

47

41 Career development 47

Well-equipped for a career

Public Outreach 51

Advancing awareness and understanding: GSCN public outreach work

51

54 GSCN Annual Report 2016�� 54

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GSCN President K. Lenhard Rudolph on his visions for the GSCN

“The GSCN is the largest network on stem cell research in Germany”

INTERVIEW WITH K. LENHARD RUDOLPH

The German Stem Cell Network (GSCN) faces some major challenges in 2017. The main task now is to secure the achievements of the last years for the medium and the long term. This will require a concerted effort from all sides. As active president, K. Lenhard Rudolph will be in charge of structuring this process this year. The work of the GSCN over the last four years, including the GSCN annual conferences as the highlight of the scientific year and a wealth of other activities, is held in high regard on a national and international level. This reputation needs to be maintained and consolidated further. In an interview with the GSCN annual magazine, K. Lenhard Rudolph spoke about his visions, plans and objectives for the network. GSCN Annual Magazine: What does the German Stem Cell Network mean to you? K. Lenhard Rudolph: For me, it is above all a network that brings together researchers from all fields of stem cell research. The GSCN is an essential platform for intensifying collaboration, developing new ideas and alliances, and initiating new interdisciplinary approaches. This is where researchers meet to share new unpublished data and to push the field ahead.

The GSCN Annual Conference is the number one gathering in Germany and Europe for the stem cell research community. The conference has a very important catalyst function in Germany because this is where alliance projects are initiated. The GSCN is the platform that brings key people working in the field together. It allows us to develop new concepts within Germany and to position ourselves jointly for international projects. Of course it is also important to participate in other international meetings to meet colleagues from abroad and keep up with the latest developments in research outside of Germany.

Photo: GSCN

As president of the GSCN, what are your objectives for 2017?

K. L. R.: It is important to me that the inspiring nature of the GSCN – with around 400 stem cell researchers participating in the annual conferences – is maintained and used even more effectively. I would like to give additional weight to the conference formats where everyone sits together


and discusses themes that go beyond the individual working groups and plenary sessions. There is a big question mark hanging over the future of the network. What do you consider feasible? What makes most sense?

K. L. R.: Stem cell research is a very important research area to further our understanding of organ function maintenance, aging, and the development of disease and is thus hugely relevant to society. The GSCN is the largest network for stem cell research in Germany and the most important platform for the scientific advancement of this field. The continued operation of the GSCN is therefore a high-interest issue. Members of the GSCN board are in ongoing dialogue with various research institutes and the Federal Ministry of Education and Research to explore all possible options to continue the work of the GSCN post 2017 and find a viable solution. The GSCN has published a white paper on stem cell research. What response can we expect from policymakers and what can policymakers expect from us?

K. L. R.: The white paper illustrates the dynamics and potential of stem cell research. Public debate is also increasingly focusing on the future areas of application of this research. It is now time to use these opportunities and establish Germany as a major location in the international arena in this research area for the long term. This needs to be understood and backed by policymakers. The main objective of our paper was to point out these opportunities and recruit the political support to make the most of them. What changes would you like to make to the GSCN Conference?

K. L. R.: I would like to further promote scientific exchange between all participants and address the research themes more intensively in the plenary sessions so that we can discuss them all together. Of course I would like to keep the focus on contributions from German research institutes, but I would also like to increase the international integration of the GSCN, particularly with our partners in Europe. The GSCN Conference is the ideal platform for this endeavor.

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INTERVIEW WITH K. LENHARD RUDOLPH

Karl Lenhard Rudolph is scientific director of the Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) in Jena, professor for molecular research on aging at the Friedrich Schiller University Jena (FSU), former president of the German Association for Aging Research (DGfA) and, since September 2016, active president of the German Stem Cell Network (GSCN). The renowned researcher on aging and physician has received many awards for his work, including the Leibniz Prize in 2009 and the German Cancer Award of the German Cancer Society in 2015. His main research area is the origins, processes and consequences of stem cell aging. Rudolph’s research findings have been published in well over 150 publications in reviewed international journals, on subjects including the clonal dominance of mutated stem cells, telomere shortening in stem cells and the influence of external factors such as nutrition on stem cell functionality.

K. L. R.: The focus this year is on the aging of stem cells. There is increasing evidence that age-related loss of function and mutations of stem cells can cause dysfunctions and disease in old age. Other emerging areas are the impact of commensal bacteria in the gut, for example, on stem cell function, computer-assisted approaches in stem cell analysis and the individualized prevention of diseases based on stem cell changes. What basic themes would you like to advance in stem cell research?

K. L. R.: I would like to advance our understanding of the connection between stem cells and aging. And there are very practical reasons for this. For one thing, mutations in stem cells expand clonally in old age. Around 50 percent of people aged over 70 are affected by this and it impacts both on their life expectancy and the probability that they will develop a disease. In my opinion, this means we should be taking a very close look at stem cells in these processes. Another aspect concerns the extent to which the aging of stem cells influences the development of cancer and can be identified as a cause of the disease. That would affect all organs and tissues although research here has until now been limited to the hematopoietic system, i.e. blood production. This is a big emerging field.

Stem cell clones that expand and exhibit gene mutations have been shown to exist, and we know that they grow with increasing age, but we have no idea why that is so. What are the selection mechanisms and what impact does lifestyle have? Is it possible to slow down the rate of clone mutation? I would be interested to find out what role sports, movement and nutrition have here – these are all extremely exciting topics with regard to the origin and development of mutations. Even if these topics don’t seem to have much to do with stem cells at first glance, they do have an impact on them. An example is the microbiome. We have initial evidence that the colonization of the gut affects stem cells. I would like to add a systems biological approach here.

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Stem cell research is, in its very nature, a crosscutting field of research and as such extremely important. While stem

cells are a rare type of cell, they are important and I believe it is crucial to further our understanding of them. Not only are they the foundation of life for maintaining organisms, they also influence the regenerative capacity of our organs as we get older. What has been the most important research finding for you over the past few years?

K. L. R.: For me it is the finding that mutated clones are not a rarity but are in general a part of the biology of the aging human. There is evidence that these clones should not just be regarded as biomarkers but have a causal connection to the development of disease in old age. This is a whole new field of research in my opinion as it opens up the possibility of endogenously influencing the body’s own stem cells with targeted medicine in order to prevent or at least slow down the development of disease in old age. Another important new area of research is based on experiments that show that changes in the epigenome in old age lead to a malfunctioning of stem cells thereby reducing organ function and regeneration. Researchers from the US have now been able to show that epigenetic changes of this kind are in principle reversible which could, in turn, prolong the maintenance of organ function in old age. This is also a very promising approach in my opinion. What are the highlights for the GSCN in 2017?

Our annual conference in Jena from 11 to 13 September will of course be a big highlight for us. We are preparing a first-rate program that will include very interesting keynotes, great locations and lots of exciting events. I hope that a large number of researchers will come to our open and academically rigorous Jena. I am also already looking forward to this year’s edition of UniStem Day, an exciting event with high-school students that really impressed me last year and will take place on an even bigger scale in Germany this year. Beyond that, our working groups are becoming increasingly active and there are lots of different workshops in the pipeline, a Gordon conference on stem cells, the NRW meeting in May, supported by the GSCN, and the ISSCR in Boston, in which the GSCN will also be participating again. This wealth of activities shows just how vital and dynamic our network continues to be in 2017.

Photo: GSCN

Which themes could the GSCN expand on further in future?


FROM GSCN CENTRAL OFFICE

GSCN News Stem cell films for events In the last three years the GSCN has made eight short films on German stem cell scientists and their research. The eight stem cell researchers portrayed so far are Magdalena Götz, Anthony Ho, Andreas Trumpp, Hubert Serve, Andreas Zeiher, Tobias Cantz / Michael Manns, Nils Hoppe and Ulrich Martin. New films planned for 2017 will feature K. Lenhard Rudolph, Claudia Waskow and Jürgen Knoblich. The films provide an insight into current research on heart, blood, liver and neuronal diseases and the corresponding stem cell research. All film portraits are available in English and German and are ideally suited for presentation at public events. They are available on the GSCN website under the “Resources” tab.

Photo: GSCN

Travel Awards – an example from ISSCR 2016

Via its working groups, the GSCN grants travel awards to young scientists wishing to take part in a conference or workshop with a poster presentation. And it’s well worth the effort. Stefan Hauser from Tübingen was one of six recipients of a travel grant to the ISSCR Annual Meeting 2016 in San Francisco. Here is an extract from his report: “One of the most inspiring talks for me was the presentation by Shinya Yamanaka. The first part of his talk “Reprogramming

of Cells and Scientist” focused on a more personal level on the discovery of iPSCs and how this changed his scientific life. He said that “iPSC discovery reprogrammed myself” and led to “spending a lot of time talking with people in government and industry and banks, and also spending a lot of time on fund raising … But some portion of myself is refractory to reprogramming. That part tells me I should enjoy basic research.” This part was quite inspiring to me and is important for the translational aspect of stem cell research. … Another highlight of the ISSCR annual meeting was the poster session every evening where hundreds of projects were presented in parallel. Several encounters with poster presenters led to fruitful discussions, insights into adjacent fields of research, ideas for my own research, and potential contacts and cooperation for the future. Apart from ‘pure’ science, it was fantastic to join the GSCN WunderBar Evening. The German stem cell scientists met at the ‘Thirsty Bear Brewing Company’ and had a great evening with inspiring scientific as well as non-scientific discussions, great beer and tapas in a relaxed atmosphere which led to new cooperation and ideas and was a helpful way to meet new people and get to know each other better.” There are now four fixed dates a year to which GSCN members and researchers in Germany can apply for travel grants to international stem cell conferences: by 28 Feb. for events taking place from 1 April to 30 June, by 31 May for events from 1 July to 30 Sept., by 31 Aug. for events from 1 Oct. to 31 Dec. and by 30 Nov. for events from 1 Jan. to 31 March the following year. Applications should be sent to the GSCN central office by the respective deadline. They should include a letter of motivation and the contribution submitted for the event in question.

Leibniz Institute on Aging - Fritz Lipmann Institute (FLI) Research for better aging

The Leibniz Institute on Aging – Fritz Lipmann Institute (FLI) has dedicated to biomedical aging research since 2004. More than 330 members from over 30 nations explore the molecular mechanisms underlying aging processes and age-associated diseases. It is one of only two national research institutes on basic mechanisms of aging in Germany. The main aim of research at FLI is to delineate how aging leads to the development of tissue dysfunction and diseases in the elderly. If the understanding of the aging process contributes to the extension of healthy lifespan, the strains on society can be Annual GSCN Magazine 2016/17

minimized and the society’s future development will be enriched by the wealth of knowledge and experience older people possess. As one of 91 institutes of the Leibniz Association, the FLI is publically funded by the German Federal Ministry of Education and Research (BMBF) and the State of Thuringia. Leibniz Institute on Aging/ Fritz Lipmann Institute (FLI) Beutenbergstraße 11 · 07745 Jena www.leibniz-fli.de

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GSCN Awardees 2016 (from left): Leo Kurian, Claudia Waskow, Daniel Besser, Anar Deep Sharma, Ulrich Martin, Guangqi Song, Martin Pacher

In 2016, the GSCN Young Investigator Award went to Dr. Leo Kurian from the Center for Molecular Medicine Cologne (CMMC) at the University of Cologne. The recipient of the GSCN 2016 Female Scientist Award was Prof. Dr. Claudia Waskow from the TU Dresden. The GSCN 2016 Publication of the Year Award honored Dr. Guangqi Song, Dr. Martin Pacher, Prof. Michael Ott and Dr. Amar Deep Sharma from the REBIRTH Center and the TWINCORE Center of the Hannover Medical School (MHH) for the publication “Direct Reprogramming of Hepatic Myofibroblasts into Hepatocytes In Vivo Attenuates Liver Fibrosis” in the journal Cell Stem Cell.

Wunderbar: GSCN at the ISSCR in San Francisco First Stockholm, then San Francisco: The GSCN organized its second WunderBar Evening at the Annual Meeting of the ISSCR in 2016. The networking meet of GSCN members, friends and guests in San Francisco was a great success. Ninety guests attended the evening event that was held in a local brewery and provided lots of opportunity for personal networking. The 2017 ISSCR Annual Meeting will take place in Boston and the GSCN will certainly be holding another edition of the WunderBar Evening there.

Trouble shooting – Non-PI Meeting in Hannover

In the follow-up to the GSCN Conference in Hannover, 23 non-PIs met to discuss trouble shooting in research, to report on methods, ideas and stories about research failures and lab crises, and talk about these together in a joint forum. The meeting, held under the motto “learning from mistakes”, gives scientist the chance to share their experiences and learn from each other. The response to this second non-PI meeting of the GSCN was very positive and work has started on preparing future meetings on themes relevant to young scientists.

Explaining and discussing regulations – GSCN-PEI Workshop “This was a highly informative workshop on translation, clinical trials and the many regulatory issues that we as scientists have to observe,” says GSCN managing director Daniel Besser, reporting on the information event on regulatory processes hosted by the Paul Ehrlich Institute (PEI) as a one-day workshop in November 2016. The participants found the clarification of the regulatory procedures involved in translation extremely helpful, as it gave them lots of pointers on how to save time and money in application procedures. The PEI advises scientists on how to effectively and successfully apply for clinical trials.

Grant-Writing Workshop – watch out reviewers!

Twelve young scientists met in Ulm for two days to practice writing grant applications and learn tips and tricks to make their applications to the EU and other funding bodies successful. Hartmut Geiger, who organized the workshop, reported: “The Career Development working group of the GSCN (Insa Schroeder, Hartmut Geiger) held a grant-writing workshop in November in Ulm. It was booked out very early on and the participants told us that it was very helpful. We hope that all participants will be able to put what they learned to use in the near future and be successful in their applications. Watch out reviewers, from now on all applications for stem cell research will be perfectly worded!”

Non-PIs exchanged views on trouble shooting in the lab in Hannover 12

Photos: GSCN

GSCN Awards 2016



Photo: DGTI/ Thomas Ecke

Satellite sessions and supporting conferences As in previous years, the GSCN was very busy in 2016 presenting and promoting stem cell research at the conferen ces and meetings of other associations. The GSCN helped prepare two sessions at the conference of the Interdisciplinary Group for Laboratory and Flow Cytometry (IGLD) that took place in February 2016 in Hamburg. Speakers in a session on organs and organ models from stem cells were: • Magdalena Renner, IMBA, Wien: Embryonale menschliche Gehirne aus Stammzellen • Tobias Cantz, Hannover Medical School: Reprogrammierung somatischer Zellen für innovative Leberzell-Transplantate • Sina Bartfeld, Inst. f. Molekulare Infektionsbiologie, Würzburg: Infektion, angeborene Immunität und Krebs des Magens – Organoide aus Stammzellen als neues Modellsystem • Robert Zweigerdt, Hannover Medical School, Hannover Myocardiale Regeneration durch pluripotente Stammzellen • Gabriele Brachtl, Paracelsus Medical University, Salzburg: Organregeneration und Immunmodulation • Peter Frost, Pelobiotech, Planegg: Magnetisches Bioprinting für die personalisierte Therapie The lectures on applied stem cell research in the second session were: • Guido Moll, Charite, Berlin: Therapeutische Mesenchymal Stromale Zellen: Sicherheit und Effizienz nach systemischer Infusion • Stefan Radtke, Fred Hutchinson Cancer Research Center, Seattle: Hämatopoetische Stammzellen: Vom Menschen zum Affen • Dirk Strunk, Paracelsus Universität, Salzburg: Welche MSC für welche Anwendungen oder Wie wird Fett zu Knochen? • Gerhard Fritsch, Medizinische Universität Wien: Flow Analysen nach Kryokonservierung: Muster ohne Wert? • Karen Bieback, Institut für Transfusionsmedizin und Immunologie, Med. Fakultät Mannheim: Not to get lost in translation: Mesenchymal stromale Zellen vom Labor ans Krankenbett At the 49th Annual Meeting of the GSCN partner organization German Society of Transfusion Medicine and Immunohematology (DGTI) held in September 2016 in Nuremberg, the GSCN organized another successful satellite session, as it had already in 2014 in Dresden and in 2015 in Basel. Speakers at the session were: • Gerald Schumann, Paul Ehrlich Institute, Langen: Reprogramming triggers mobilization of endogenous transposable elements in human induced pluripotent stem cells – consequences for host gene expression • Robert Zweigerdt, Hannover Medical School: Myocardial regeneration by human pluripotent stem cells


From left to right: Robert Zweigerdt, Daniel Besser, Karen Bieback, Thomas Brabletz, Susanne Kleber, Gerald Schumann and Dirk Strunk.

• Thomas Brabletz, Universität Erlangen: Metastasis: cancer stem cells, microRNAs and EMT • Susanne Kleber, DKFZ Heidelberg: Cancer stem cells in brain tumor initiation and progression In February 2016, the first international symposium of the ISSCR in Germany took place in Dresden. The GSCN supported the event financially and logistically, through its members on the program committee, through its participation in evaluating the submitted contributions and by holding a very successful breakout session on 3D cultures and organoids with Julia Ladewig (Bonn), Michael Karl (Dresden), Jürgen Knoblich (Vienna, Austria) and Motosugu Eiraku (Kobe, Japan).

PluriCore Network Meeting in Berlin

May 2016 saw the second meeting of the PluriCore Network. Forty-one experts on human iPSCs from 20 institutes convened in Berlin with the objective of elaborating guidelines for quality assurance in the transfer of cell lines and in cells and tissues earmarked for reprogramming. Other topics on which the researchers shared their experiences included the reprogramming, differentiation and genome editing of pluripotent stem cells. Guest speakers from the Salk Institute in San Diego, the Robert Koch Institute and the Max Planck Institute in Munich reported on the latest developments in core facility management, methodology and ethical issues. Based on the findings of the meeting, a standardized transfer form was developed that contains the most important information on cell and tissue samples, as well as templates for consent forms and for information and ethics sheets for donors taking part in iPSC trials. These are available on PluriCore Network’s website (www. gscn.org/de/RESSOURCEN/DeutscheStammzell-CoreEinheiten.aspx).

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Take CARE – Hans Schöler’s Institute to open in Munich

GSCN and Schering Foundation develop teaching materials for schools on stem cells The Schering Foundation and the GSCN have developed four teaching modules on current stem cell research for senior high-school students. The teaching material is freely accessible for everyone in digital form and can be used by both teachers and students in class. The modules are designed in a conference format and aim to close the gaps between current stem cell research, genetic engineering, applied research and the presentation of stem cells in standard school biology books. The material is available for download at www.stammzellen-verstehen.de.

UniStem Day 2016 & 2017

Scientists at the new Center for Advanced Regenerative Engineering (CARE) will be working on developing technologies and therapies for the medical application of stem cells. The Bavarian government is providing €25 million of funding for the center, which is scheduled to open in 2017 in Munich. The CARE research institute will be pursuing new approaches in regenerative medicine and researching into medicinal drugs.

First Max Planck Center for Regenerative Biomedicine opens in China

Scientists at the newly opened Max Planck – GIBH Joint Center for Regenerative Biomedicine in Guangzhou have big plans – they want to obtain nerve, heart and lung cells from reprogrammed stem cells. The new institute is anticipating a high level of exchange with German stem cell researchers.

French stem cell network set up

What began as a pilot project in 2016 is set to become a calendar fixture as of 2017: UniStem Day. The European day of stem cell research in 2016 was such a success in the eight participating German cities that all the institutes are keen to take part once again in 2017 and the number of registrations received is even higher than last year. On 17 March 2017, scientists and school students in Heidelberg, Hannover, Bochum, Jena, Bonn and Dresden, Berlin and Münster and other cities will once again be spending the day teaching and learning about stem cell research. For more information, go to www.unistemday.de

The French stem cell network, Société Française de Recherche sur les Cellules Souches (FSSCR), was founded on 7 Nov. 2016, in Paris. GSCN managing director Daniel Besser advised the network during the founding process.

EuroStemCell website relaunch

Basic and well-researched facts and information on stem cells, research and therapy approaches are available on the website www.eurostemcell.org. The website has now been redesigned and is available in six languages. A visit is highly recommended!

Max Planck Institute for Heart and Lung Research MPI-HLR

The Max Planck Institute for Heart and Lung Research, located in Bad Nauheim, investigates developmental processes of organs in the cardiovascular system and the lung.

A second focus is molecular and cellular processes during the formation of diseases in heart, blood vessels and lung, including remodeling processes in these organs. Scientists at the institute search for new approaches to support repair and regeneration of the affected organs. 14

The MPI closely cooperates with universities in Frankfurt, Gießen and Marburg. It has become a major part of various federal and state excellence initiates and contributes to two “Gesundheitsforschungszentren”.

Max Planck Institute for Heart and Lung Research W.G. Kerckhoff Institute Ludwigstr. 43 61231 Bad Nauheim www.mpi-hlr.de


Are You a True Master? Cell culture work, which includes seeding, cultivation, and analysis, is a special part of daily laboratory routine. Whenever cells are involved, experimental conditions are as different as the cells themselves. This especially applies to stem cells. The worst scenario in the lab: your valuable cells are contaminated. Check your expertise in cell handling and get some tips and tricks. www.eppendorf.com/cellexperts

Eppendorf ® and the Eppendorf Brand Design are registered trademarks of Eppendorf AG, Germany. All rights reserved, including graphics and images. Copyright © 2017 by Eppendorf AG.

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4TH ANNUAL CONFERENCE OF THE GSCN

4th Annual Conference of the German Stem Cell Network from 12 – 14 September, 2016 in Hannover

Novel trends and technologies in stem cell research

O

nce a year, the German Stem Cell Network (GSCN) brings together researchers from across Germany for a few days of intensive scientific exchange. This year’s three-day conference was held at Hannover Medical School (MHH) and revolved around new techniques, results and knowledge in stem cell research. The researchers made the most of the plentiful opportunities for lively discussion and debate at the poster presentations, sessions, plenary symposia and evening events. An industry exhibition was held in parallel, giving researchers the chance to network with corporate lab suppliers and specialists in cell culture technology and molecular biology. The event has grown from year to year and in 2016 it consisted of 35 booths spread over several stories.

On Monday, Minister-President of Lower Saxony Stephan Weil, opened the conference with a warm welcome and proved to be very well-informed on stem cell issues. Following brief opening addresses by MHH President Christopher Baum and GSCN President Uli Martin, the conference started off with some exciting news. Keynote speaker Alexander Meissner announced that he is leaving the Broad Institute in Cambridge (US) and coming to Berlin in

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2017. As director of the Max Planck Institute of Molecular Genetics he will be in an excellent position to contribute to German stem cell research. In his lecture, he presented interesting new data on mechanisms of epigenetic regulation in stem cells and over the course of their development. It turns out that few CpGs show changes in their methAlexander ylation patterns during normal Meissner early embryonic development. Regions generally lie far above of developmentally regulated genes, and yet play important roles in their expression. In the second opening keynote of the conference, Sean Morrison from UT Southwestern, Texas (US), reported on findings in blood stem Sean cells and their interactions with the Morrison perivascular stem cell niche. Morrison presented the latest data on the function of the chemokine CXCL12 in Tcf21-positive stromal cells and their role in establishing a niche for hematopoietic stem cells. The leptin receptor regulates the differentiation of stem cells of the bone in osteoblasts and adipocytes in the bones of the limbs. Leptin/Leptin-R activates the Jak2/Stat3 signaling pathway and promotes adipogenesis. Morrison also addressed new findings on the role of osteolection (CLEC11a) in the maintenance of the adult skeleton. The findings shed light on the regulation of bone homeostasis and how the niche for hematopoietic stem cells is established and maintained in the bone marrow. On the first evening of the conference, Hiroshi Nagashima from Meiji University in Tokyo, Japan, gave a lecture on the generation of human organs in pigs. This branch of research has become increasingly important in the last few years due to the shortage of donor organs available for transplantation. However, the ethical implications of these technologies remain controversial. Hiroshi Nagashima’s presentation focused on his lab’s efforts to grow a human pancreas in a pig model. By changing the gene expression of Pdx1-Hes1 (the Pdx1 gene plays a key role in the formation of the pancreas), a genetic model was developed in which the animals no longer form a pancreas of their own. Exogenous stem cells from normal pigs, which differentiate into pancreatic cells, were able to completely form the organ during embryonic development, allowing the genetically modified pigs to survive. The team is now planning to generate models for other organs. The long-term objective is to use human cells to generate “humanized” organs in pigs, but this still requires a number of technological and

Photos: GSCN

This year’s GSCN Annual Conference in Hannover proved once again to be the most important annual meeting for stem cell researchers in Germany. Around 400 scientists met in the Lower Saxon capital for three days of intense communication and exchange on recent developments in the field. The top themes were the latest trends and techniques in organoid technologies, which are maturing at a rapid pace, the “new” discovery of extracellular vesicles, and tissue engineering. Ethical considerations were a major topic in a symposium held in parallel to the conference. A new component of this year’s GSCN meeting was a technology transfer exchange.



ethical issues to be resolved. Another important lecture Peter Zandstra presented impressive progress on how the on a new animal model was held by Thomas Eschenhagen design of “in vitro niches” combined with computational from the Medical Center Hamburg-Eppendorf (UKE) as modeling of “stem cell behavior” can be applied to direct part of the Presidential Symposium. EschenhaPSC differentiation into hemogenic mesoderm, and gen presented data from his working group on ultimately mature T-cells. Moreover, once blood the transplantation of engineered heart tissue progenitors have emerged, successful mainte“New treatments (EHT) differentiated from induced pluripotent nance of these progenitors in a “blood forming for cardiac stem cells (iPS cells) and endothelial cells in niche” was demonstrated, reminiscent of the infarction” guinea pigs. The animals were transplanted endogenous hematopoietic stem cell niche in with human EHT seven days following injury to the body. In conclusion, Peter highlighted how the cardiac muscle. After 28 days under immunoengineering principles and theoretical modeling suppression, the transplanted cardiac muscle tissue can be successfully applied to the very practical chalin the scarred tissue had grown, vascularized and formed lenges of translational stem cell research, providing imporsome electrical connections. The findings show that human tant stimulation to the field. 3D heart tissue can be built into the injured heart and raises hopes that this could lead to new therapies in treating Pete Coffey‘s lecture was canceled due to illness; two young heart attacks. researchers jumped in with excellent presentations. Boris Greber from the Max Planck Institute for Molecular BioBoth areas – basic research and clinical translation – re- medicine in Münster gave a lecture entitled “Principles of quire a better understanding of the complex cellular and cardiac induction in human pluripotent stem cells” and molecular clues underlying pluripotency and linage-spe- Chao Sheng from the Institute of Reconstructive Neurobicific differentiation. This complexity is further extended by ology of the University of Bonn spoke on “Blood-derived the diversity of 2D and 3D culture platforms applied in the stable induced neural stem cells: Preservation of age-refield. Focusing on the transition of pluripotent stem cells lated DNA methylation patterns and application to disease (PSCs) into definitive blood cells, in his keynote lecture, modeling.”

The REBIRTH Cluster of Excellence From regenerative biology to reconstructive therapy REBIRTH has, under the nationwide Excellence Initiative, been funded as a cluster of excellence since 2006. The aim of the internationally renowned centre for regenerative medicine is to develop innovative therapies for the heart, liver, lungs and blood, and to translate these into clinical use. This involves collaboration – in Hannover and at participating partner institutions – between physicians, physicists, chemists, biologists, engineers, legal professionals and ethicists, the main research priorities being stem cell biology, the reprogramming of cells for cell therapy, disease models and tissue engineering.


Participating Partners: • Hannover Medical School • Leibniz University of Hannover • Hannover Laser Centre • University of Veterinary Medicine Hannover, Foundation • Helmholtz Centre for Infection Research Braunschweig • Max Planck Institute for Molecular Biomedicine, Münster • Institute of Farm Animal Genetics, Friedrich Loeffler Institute, Mariensee • Fraunhofer Institute of Toxicology and Experimental Medicine, Hannover

Exzellenzcluster

REBIRTH Cluster of Excellence Hannover Medical School Carl-Neuberg-Straße 1, 30625 Hannover www.rebirth-hannover.de

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A pioneering feature of the GSCN conferences is the confirms this view.” In 2016, 184 abamount of the program dedicated to talks by up-andstracts were submitted for the concoming young scientists. GSCN working groups ference and evaluated by a jury. select a program of presentations from the best The chosen papers were organabstracts for concurrent sessions. The particized into a total of 14 sessions “Young scientists ipants of the online evaluation of the conferreflecting current trends and top play a ence were full of praise for this approach, with themes in stem cell research. The major role“ 79 percent rating the structure of the conferfield of organoids is still developing ence as “very good” or “excellent”. “For the 2017 exponentially and becoming increasingconference in Jena, we will try to organize even ly differentiated into subfields for each organ. more plenary sessions alongside the Presidential Symposium and the keynotes,” said GSCN managing direc- Beside a complete session on organoids in “Technologies in tor Daniel Besser, “but the basic structure of the conference stem cell research”, Alexander Kleger (University Medical is our trademark and also provides a great opportunity for Center, Ulm) presented a novel approach to direct human young researchers to present their data. The survey clearly pluripotent stem cells towards pancreatic organoids (POs) resembling acinar and ductal progeny in the session “Tissue engineering and organoids”. Upon orthotopic transplantation into the murine pancreas, these POs formed normal pancreatic ducts and acinar tissue resembling fetal human pancreas. By applying this differentiation platform to model pancreatic facets of cystic fibrosis (CF), the group was able to demonstrate that pancreatic commitment occurred unhindered in CF patient-derived iPS cells both in vitro and in vivo. Interestingly, the cells mirrored the CF-phenotype on a functional and global gene expression level and can thus be used for drug screenings and the testing of new therapeutic approaches.]. Further, Rasmus Freter (LICR, Oxford, UK) introduced his stem cell reporter OSCAR in the working group session “Somatic stem cells and development”. The lab has shown previously that adult stem cells of at least seven different lineages show decreased rates of mRNA transcription, marked by dephosphorylated RNA polymerase II. Using a phosphorylation-sensitive yellow fluorescent protein (YFP) that loses fluorescence in activated

Max Delbrück Center for Molecular Medicine in the Helmholtz Association (MDC) Excellent stem cell research at the MDC in Berlin The MDC is a biomedical research center in the north of Berlin. Many of its research groups work with stem cells, which often serve as a model system for the investigation of the molecular causes of diseases of the cardiovascular system, the nervous system or the immune system, cancer and developmental disorders. Also, the application in therapy is being investigated. The center‘s Scientific Director Prof. Martin Lohse says: „We are very well-connected with clinical researchers and offer excellent infrastructures for stem cell research and animal ex18

periments. This makes the MDC an excellent place for working with stem cells. We will even expand our expertise in the field in the near future.“ The Berlin Institute for Health (BIH), which was founded by MDC and Charité, will also strengthen its stem cell research by recruiting scientists for the areas of humanized models systems and cell engineering. A core facility for induced pluripotent stem cells (iPS cells) is maintained by both MDC and BIH and provides the scientific staff with support and expertise in obtaining and modifying iPS cell lines.

Max Delbrück Center for Molecular Medicine (MDC) Robert-Rössle-Str. 10, 13125 Berlin www.mdc-berlin.de



cells, it was possible to visualize dormant adult stem cell induction and differentiation in intestinal organoids using timelapse microscopy and FACS. This reporter will be useful for the identification and isolation of pure dormant stem cells from many tissues as well as the screening of culture conditions for the expansion of immature stem cells in vitro. MSCs have been applied in many clinical trials to treat various diseases. In contrast to the original hypothesis that MSCs home and integrate into affected tissues, in many diseases they seem to exert their therapeutic functions Hiroshi in a paracrine rather than a cellular manNagashina ner. In the session “Stem cells in regenerative therapies” Verena Börger (University hospital Essen) presented data showing that extracellular vesicles from MSCs, such as exosomes and microvesicles, can exert comparable therapeutic functions in several disease models as the MSCs themselves. The researchers are currently focusing on improving their MSC-EV production and quality assurance platform with the aim of applying for a MSC-EV production license in near future.

The program of the GSCN annual conference covered the whole thematic spectrum of the working groups from cancer stem cells to pluripotency. Birte Baudis (Institute for Neurophysiology, Cologne) reported in the session “Stem cells in regenerative therapies” on the immunologic properties of murine embryonic stem cell (ESC)-derived cardiomyocytes (CMs) in immunocompetent mice mismatched for major (MHC) or minor histocompatibility antigens (mHAg). She found that eight weeks after transplantation the survival of ESC-CMs transplanted under the kidney capsule was comparable in both experimental groups and in immunodeficient mice. Surprisingly, the immunization of mice with the mHAg expressed by ESC-CMs did not reduce the CM survival although it induced mHAg-specific cytotoxic T cells (CTLs) and caused rejection of control cancer cells that expressed the same mHAg. In vitro analyses demonstrated that this apparent “immunological privilege” of ESC-CMs in vivo could be due to very low levels of MHC molecules expressed on the surface of ESC-CMs and their reduced susceptibility to lysis by CTLs. Aline Bozec (Erlangen, Germany) reported in the session “Stem cells and aging, genome stability and epigenetics” on how a high fat diet changes the hematopoietic stem cell (HSC) bone marrow niche. Mechanistically, diet-induced changes of the intestinal microbiota, particularly gram+ bacteria, induced a switch of mesenchymal stem cells from osteoblasts to adipocytes, which consequently alter HSC differentiation.

Center for Regenerative Therapies Dresden (CRTD) DFG Research Center and Cluster of Excellence at the TU Dresden At the DFG Research Center for Regenerative Therapies Dresden (CRTD), Cluster of Excellence at the TU Dresden scientists are seeking to understand the mechanisms of regeneration using model organisms to translate the results to man and to develop novel regenerative therapies for thus far incurable diseases. The center’s major research areas are focused on hematology/ immunology, diabetes, neurodegenerative diseases, bone regeneration and technology development. Currently, seven professors and twelve group leaders are working at the CRTD. They are integrated into a network of over 80 member labs at Annual GSCN Magazine 2016/17

7 different institutions in Dresden. In addition, 21 partners from industry are supporting the research projects. The synergies in the network allow for a fast translation of results from basic research to clinical applications. DFG Research Center for Regenerative Therapies Dresden – Cluster of Excellence TU Dresden Fetscherstrasse 105 · 01307 Dresden www.crt-dresden.de

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Not all the lectures in Hannover were dedicated to basic science – many focused on legal, ethical and philosophical aspects of stem cell research. A special symposium gave researchers the opportunity to discuss how artificially generated “totipotent” cells should be viewed in the context of current definitions of embryos Thomas Eschenhagen in German law. “The symposium on ‘Totipotent non-embryos and non-totipotent embryos’ certainly delivered on its provocative title,“ said Martin Heyer from the Institute of Science and Ethics at the University of Bonn. „The exciting issues involved in the hotly debated topic of totipotency were discussed in depth and at a high level by the speakers and the audience. The fact that the event was part of the GSCN Annual Conference made it particularly successful.” Following a lecture by Thomas Eschenhagen (UKE, Hamburg) on heart muscle cells in disease modeling, “Engineered human heart muscles for disease modeling and cardiac repair” (see above), the central Presidential Symposium presented the winners of the GSCN Awards. The winner of the Young Investigator Award 2016 Leo Kurian (University of Cologne) spoke about his lab’s work in the field of developmental biology on non-coding (Inc) RNAs and their significance in inducing the embryonic development of the heart. “I am delighted to be recognized by the German Stem Cell

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Network. I would like to thank my lab, to whom the credit really belongs for the work we do and to GSCN for the award. This was my first GSCN meeting and in my opinion this is a great forum to learn about national research efforts and a great platform for networking. I am particularly impressed with the diversity of the groups and excited about the excellent science presented,” said Leo Kurian on receiving the GSCN award.

The GSCN Female Award 2016 went to Claudia Waskow (TU Dresden). “I am delighted about the award and regard it as an exceptional distinction for the work that my team and I have been able to conduct in the last few years,” said Claudia Waskow about the award that recognizes her outstanding scientific achievements. She held a lecture entitled “Generation and regeneration of human and murine hematopoietic stem cells”.

The GSCN Publication of the Year 2016 award went to Guangqi Song, Martin Pacher, Michael Ott and Amar Deep Sharma of the REBIRTH Center and the TWINCORE Center of the Hannover Medical School (MHH) for their publica-



tion “Direct Reprogramming of Hepatic Myofibroblasts into Hepatocytes In Vivo Attenuates Liver Fibrosis” published in the journal Cell Stem Cell. Guangqi Song held a lecture with the same title as the publication at the GSCN conference. Their article impressively demonstrates how Shinya Yamanaka’s work on reprogramming has given rise to a technology that now enables the direct conversion of a cell of one type into other cell types in the organism. These approaches could revolutionize the treatment of many severe diseases in the future.

• Antje Appelt-Menzel, University of Würzburg, TERM: “Establishment of a human blood-brain barrier co-culture model based on human multipotent and pluripotent stem cells mimicking the neurovascular unit” • Christoph Hirche, German Cancer Research Center Heidelberg (DKFZ)/ HI-STEM gGmbh: “MCMV infection modulates cell cycle state and functionality of long-term hematopoietic stem cells in vivo” • Alexander Kleger, Ulm University: “Human pluripotent Both poster sessions triggered lively discussion and destem cell-derived acinar/ductal organoids generate hubate. A total of 150 posters were presented in sections corman pancreas upon orthotopic transplantation and alresponding to the different working groups. The informalow disease modeling” tion displayed wasPROGRAM studied with -great MHH Hannover: “Reprogramming en• Maike COL21693-StemFlex - CONF Halfinterest. Page - The Trim:poster 210 x 148 mm Kosanke, - 4C awards provided by GSCN member company Peptrotech, riches for subchromosomal variants that pre-exist at low went to: frequency in parental cells”

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The scientific program of the conference was rounded off with a REBIRTH session addressing the whole range of ethical and legal aspects of stem cell research from basic research to heart development and the treatment of heart disease, with presentations by Nils Hoppe, Leibniz Universität Hannover, and Kai Wollert, Thomas Thum and Robert Zweigerdt from the Hannover Medical School. The GSCN conference prides itself on further improv- High-ranking public event in Hannover at the conclusion of the ing its format and its program of events conference (from left): Michael Manns, Nils Hoppe, Tobias Cantz, Stefanie Seltmann, Uli Martin and Axel Haverich discuss the every year. The Program Committee potential use of stem cell therapies. thus followed the call to offer even more “meet the expert” tables, where small groups are given the was exciting because we had some great projects and good opportunity to fire questions discussions. Over time and once the event has become at “experts” during the lunch more widely known, this could develop into a real technolbreaks. This year’s experts were ogy transfer exchange,” said Daniel Besser, who initiated Ingo Roeder (TU Dresden), Hans the workshop. “We plan to work on developing it further.” Schöler (MPI Münster), Ana MarPeter Zandstra tin-Vilalba (DKFZ Heidelberg), Mari- A range of strategic issues was also addressed and dissa Karow (LMU Munich), Henner Farin cussed at length during the conference in Hannover. Topics (Goethe University Frankfurt) and Ina Gruh included the promotion of young scientists, clinical trials, (REBIRTH, Hannover). “We had a very interesting disregulatory issues and technologies in stem cell research. cussion with Hans Schöler,” said conference particiAlongside an excellent session on organoids by the pant Sebastian Diecke. “We didn’t just talk about working group “Technologies in stem cell restem cell research but also about career-related search”, the session on “Clinical trials and reg“We will develop issues, such as how best to acquire funding. It ulatory affairs” proved to be one of the highthe Tech-Transferwas a great opportunity to ask questions dilights of the conference. It consisted of three Exchange“ rectly and get really helpful answers.” lectures on research translation. Felipe Prosper from the University Hospital Navarra, PamA new component of the conference was the plona, spoke about European funding for translaTechnology Exchange Workshop where researchers tion relating to therapies using stem cell derivatives, had the chance to present innovative technologies to in- using his university as an example. This was followed by a dustry. Selected projects were briefly presented and their lecture by Arnd Hoeveler from the European Commission, potential for industrial application was then discussed. “It and then by Aliki Nichogiannopoulou from the European

German Cancer Research Center (DKFZ) Research for a life without cancer

The German Cancer Research Center (Deutsches Krebsforschungszentrum, DKFZ), located in Heidelberg, is a member of the Helmholtz- Association and is the largest biomedical research institute in Germany. At the DKFZ, more than 1,000 scientists work together in order to develop novel strategies aimed at improving the prevention, diagnosis and treatment of cancer. Several research laboratories investigate normal and cancer stem cells (CSCs) as well as their respective niches. The goal is to develop strategies to monitor and 22

target CSCs in primary cancers and metastasis. Together with the Dietmar Hopp Foundation, the DKFZ is a shareholder of HI-STEM, the nonprofit Heidelberg Stem Cell Institute and organizes the biannual Heinrich-Behr-Conference on „Stem Cells and Cancer“, which attracts international experts in the field. With the Heidelberg University Clinic, the DKFZ has established the National Center for Tumor Diseases (NCT), to clinically translate innovative basic cancer and stem cell research discoveries into clinical therapies.

German Cancer Research Center Im Neuenheimer Feld 280, 69120 Heidelberg www.dkfz.de


4. GSCN-JAHRESKONFERENZ

Patent Office, Munich on the burgers from the barbecue and enjoyed the lush summer patenting of stem cell-based evening far away from the lecture halls. There was ample inventions. The discussion, opportunity for networking fun, rounded off by dancing which continued well into under the full moon and a nocturnal walk through magical the following break and settings with flares leading the way back through the zoo. could have carried on It’s no surprise then that the evening was given a a lot longer, generstraight “Excellent” rating in the online evaluaated much potention. The get-together on the first evening of “Wonderful tial for discussion the conference was also a lively and relaxed evening at future GSCN conoccasion with good food and plenty of good in the zoo” ferences. discussion on a pleasant summer’s evening.

A special highlight of the Hannover conference was the GSCN Networking Evening – which was held at the zoo! In pleasant summer temperatures, the conference participants strolled through the otherwise deserted zoo, admired the wolves and monkeys, and then, with a welcome drink in hand, enjoyed watching the feeding session of two polar bears. In a setting reminiscent of a Canadian logging town, the participants observed the seals and penguins, ate ham-

The final event of the GSCN conferences is traditionally a public event in the hosting city. On the Wednesday evening in Hannover, chief physicians Michael Manns and Axel Haverich together with Ulrich Martin, Tobias Cantz and lawyer Nils Hoppe – all from REBIRTH and the MHH – made up the panel hosted by Stefanie Seltmann, DKFZ press officer, to speak about the opportunities and the future of stem cell research. In the unusual setting of a former newspaper hall of the Hannoversche Allgemeine Zeitung, the GSCN showed its new movie portraits on the work of the panel participants. The portraits on Michael Manns and Tobias Cantz, as well as Ulrich Martin and Nils Hoppe are available in English and German on the GSCN website.

Max Planck Institute for Molecular Genetics MPIMG

Research at the Max Planck Institute for Molecular Genetics (MPIMG) concentrates on genome analysis of man and other organisms. It is the overall goal of all MPIMG’s groups to gain new insights into the development of diseases on a molecular level, thus contributing to the development of cause-related new medical treatments. Work at the MPIMG is characterized by a genome-wide approach to scientific questions. In this context, the very close connection between experimental and computational methods has become a major feature of all departments 24

MPIMG

and research groups at the institute in recent years. MPIMG researchers are interested in questions of epigenetic regulation and work on a better understanding of gene regulation networks for tissue formation and homeostasis, as their dysfunction my result in numerous diseases. In this context, stem cell research is gaining increasing importance. Max Planck Institute for Molecular Genetics Ihnestraße 63-73 · 14195 Berlin www.molgen.mpg.de


5th Annual GSCN Conference 11 – 13 September 2017 Friedrich Schiller University Jena www.gscn.org

International keynote speakers Elaine Fuchs (New York) · Margaret Goodell (Austin) · Heinrich Jasper (Novato) · Manuel Serrano (Madrid) Presidential Symposium Jürgen Knoblich (Vienna) · GSCN Awardees: Young Investigator, Female Scientist, Publication of the Year Abstract submission deadline for oral presentations: 31 May Oral presentations chosen from the best abstracts

Photos: MDC/Chen; GSCN/Junge; JenaKultur/Hub; MDC/Himsel; FSU/Kasper

Scientiﬁc sessions • Pluripotency and reprograming • Somatic stem cells and development • Hematopoietic stem cells • Stem cells in diseases: cancer stem cells

• Stem cells in regenerative therapies • Stem cells in disease modeling and drug development • Computational stem cell biology

Program committee Daniel Besser (Berlin) · Ulrich Martin (Hannover) · Ana Martin-Villalba (Heidelberg) · Karl Lenhard Rudolph (Jena) · Julia von Maltzahn (Jena) · Claudia Waskow (Dresden)

Supported by

Collaboration with

screening

genetic

cell therapies

stem cell bank

career

public affairs

medicine

stem cell

drug screening regulatory affairs

disease modelling

organoids


public outreach

perspectives

ethical aspects

clinical studies

potentials

genetic engineering

stem cell banks

RESEARCH FUNDING

International Comparison:

A close look at public research funding While public funding of stem cell research is increasing steadily in the United Kingdom, Sweden, Japan and the US, stem cell researchers here in Germany have been faced with steadily dwindling resources in the last few years both from the Federal Ministry of Education and Research (BMBF) and the German Research Foundation (DFG). These are the findings of a German Stem Cell Network (GSCN) white paper1 published in September 2016. The paper concludes that Germany’s research and innovation policy needs to give greater priority to stem cell research and provide funding for a balanced mix of basic and applied research.

G

ermany is commonly regarded to be one of the leading countries worldwide in stem cell research. But are public funding schemes adequately supporting fulfillment of this scientific potential? To answer this question, the GSCN conducted a survey of the national and international research landscape. As well as gathering data and facts on research policy in Germany, the UK, the US, Sweden and Japan, the study also interviewed eight German and international stem cell experts to pinpoint the strengths, weaknesses, risks and opportunities of public research funding in the different countries.

s

ks

Photos: MPI Münster / Boris Greber; GSCN

Tangible decline in funding in Germany

The paper’s report on public funding in stem cell research in Germany presents a sobering picture. On the one hand, the federal government has visibly invested in health research with a strong focus on national centers and clusters of excellence, and non-university research has been boosted by higher levels of institutional funding. On the other hand, federal funding schemes specifically geared towards individual stem cell projects and their transregional integration has declined steadily in the last few years. Between 2009 and 2014, the BMBF spent around €167 million on funding stem cell research and regenerative medicine. The funds went to a total of 341 individual and joint projects as well as large-scale structural projects, most notably the translation centers for regenerative medicine in Leipzig, Berlin and Rostock. This corresponds to an average annual funding of €27.7 million for projects from the BMBF. Calculations of average annual values of project budgets based on the duration of funding for the respective projects reveal a clear downward trend since 2011. These figures do not include the extensive institutional federal funding for the biomedical insti1 The GSCN commissioned Berlin-based analytics specialists BIOCOM AG to carry out the basic data research for the white paper, a 26-page report consisting of a facts section and an analysis section. It can be accessed via the GSCN website or ordered in print from the GSCN central office. The paper was written and edited by Ulrich Martin, Daniel Besser and Albrecht Müller from the GSCN working group on funding.


tutes of Germany’s four large research associations (Max Planck, Leibniz, Fraunhofer, Helmholtz) or the budgets of the German Health Research Centers. The figures clearly show that stem cell research as a cross-cutting discipline has receded into the background as far as public funding policy is concerned. New calls for proposals have been few and far between since 2010. The only new BMBF funding initiative relevant to biomedical scientists was the 2015 initiative for “innovative stem cell technologies for individualized medicine” (see “Research” section for more information). The DFG is the second biggest funding body for basic stem cell research in Germany after the BMBF, providing an average of €22.5 million in funding per year for approved stem cell research projects. This annual average increases to €36 million if one includes the two DFG centers with a clear focus on stem cell and regenerative medicine in Dresden (CRTD) and Hannover (REBIRTH). Funding was at its lowest in 2014, leaving university groups, whose projects frequently rely heavily on DFG funding, with ever dwindling resources.

The conclusion drawn by the authors of the white paper in their analysis of the state of public funding in Germany is that the German government was quick to focus on translation in health research by investing primarily in translation infrastructure, such as the translation centers for regenerative medicine that have been set up in Berlin, Leipzig and Rostock since 2006 and are concerned mainly with tissue engiGSCN president Ulrich Martin neering and adult stem cells. The high with Michael Henkert, volume of funding tied up in these initiaoffice manager of Michael tives meant that the system was subsequently Kretschmer MdB not in a position to response flexibly to groundbreaking developments in stem cell research such as cell reprogramming. According to the report, the restrictive legal environment for stem cell research in Germany has been another hurdle contributing to the delay in pluripotent stem cell research. Despite these obstacles, however, there are still grounds for optimism. A solid base of expertise has been established in both basic and biomedical stem cell research disciplines in Germany that has the potential to support successful translation from bench-to-bedside for many years to come.

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RESEARCH FUNDING

Public funding of research projects covering stem cells and regenerative medicine in Germany (Mio. €) 50 48 46 44 42 40 38 36 34 32 30 28 26 24 22 20 Funding of individual or collaborative research projects and the translational centers for regenerative medicine BCRT (Berlin-Brandenburg) and TRM Leipzig Funding of individual or collaborative research projects and the DFG clusters of excellence REBIRTH Hannover and CRTD Dresden

1) 2)

Significantly declining: The curve of public funding on stem cells and regenerative medicine is progressing downwards.

Stem cells as an engine of innovation in the US, UK, Sweden and Japan Research policy in the US, Japan, the United Kingdom and Sweden takes a completely different approach. “Stem cell research and regenerative medicine are firmly established as strategic priorities in the research and economic policy of these countries and are regarded as drivers of innovation,” says the GSCN white paper. Stem cell research in these countries benefits from far more diverse and large-scale funding programs established specifically for this field. The United Kingdom, for example, has set up substantial funding schemes since

Albrecht Müller summarizes the funding situation at the universities

2012 including the UK Regenerative Medicine Programme (UKRMP) and the Cell Therapy Catapult, designed to inject new momentum along the entire chain of innovation in regenerative medicine and cell therapy. The country invests more than €150 million a year in stem cell research. Sweden selected stem cell research and regenerative medicine as one its 24 research areas of highest strategic importance in 2008. It has set up stem cell centers at universities, most notably at the Karolinska Institute in Stockholm, but also in Uppsala and Lund,

Chair Tissue Engineering and Regenerative Medicine Human vascularized tissue and organ models Our main research focus is the development of human tissue and organ models that can be used as alternative test systems instead of animal research and that allow the establishment of innovative implant structures used for future therapeutic strategies. Our models are based on vascularized carrier structures (e.g. BioVaSc®) that are reseeded with cell lines, primary cells or iPSC-derived cell types. Application of primary cells or iPSC-derived cell progenies potentially enables the establishment of functional implants that minimize the risk of immune rejections and contribute to the activation of important biological mechanisms regulating natural regeneration. 28

Culturing of our tissue and organ models in specific bioreactors ensure cellular functionality in vitro by mimicking in vivo-like microenvironmental conditions. Besides the barrier systems skin, intestine, trachea and blood-brain barrier, we also established tumor models of diverse organs. Chair Tissue Engineering and Regenerative Medicine Universitätsklinikum Würzburg Röntgenring 11 · 97070 Würzburg www.term.ukw.de

Gewebespezifische Bioreaktoren und Inkubatoren


RESEARCH FUNDING

Graphics: GSCN

EU-funding between 2007 and 2013 for stem cell research in comparative countries (Mio. €)

that receive long-term funding (a total of around €10 million in 2014). The United Kingdom and Sweden are among the most successful European countries in acquiring European Union funds. As revealed by an analysis of the EU Directorate-General Research and Innovation for the GSCN white paper, UK stem cell researchers acquired the highest proportion of FP7 health research funding (€144 million), followed by Germany with €141 million. Sweden, with a population only around a tenth of that of Germany (9.8 million compared to 81.2 million), managed to secure €43 million of EU funding.

René Röspel MdB (SPD) shows great interest in stem cell research

In Japan, where iPS technology was first scientifically documented in 2006, the further development of the field has received a large volume of dedicated state support since 2008. iPS cells are regarded as a flagship technology in health research and considered a powerful economic driver, not least because of the many key patents granted to Japanese researchers. Annual funding in Japan for iPS cell research alone amounts to around €90 million.

Leibniz Institute for Zoo and Wildlife Research (IZW) in the Forschungsverbund Berlin e.V. Evolutionary wildlife research for conservation The Leibniz Institute for Zoo & Wildlife Research (IZW) is an internationally renowned research institute of the Leibniz Association. With the mission of „understanding and improving adaptability“ it examines evolutionary adaptations of wildlife and its resilience to global change, and develops new concepts and measures for conservation. To achieve this, the IZW uses its broad interdisciplinary expertise in evolutionary ecology and genetics, wildlife diseases, reproductive biology and management in a close dialogue


with stakeholders and the public. The Department of Reproduction Management, headed by Prof Dr Thomas B Hildebrandt, develops cellular techniques for conservation. This new approach is an essential, promising option for highly endangered wildlife. For this purpose, the IZW builds up international networks on „cellular techniques“, including international expert meetings of the world‘s leading scientists in the field of „cellular techniques“, and develops new methods of securing and preserving wildlife tissue samples.

Leibniz Institute for Zoo and Wildlife Research

Alfred-Kowalke-Straße 17 · 10315 Berlin

www.leibniz-izw.de

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RESEARCH FUNDING

The four countries examined in the study all have a more liberal legal environment and invest in research across the entire range of stem cell types. They are thus the first countries where clinical trials are going ahead for therapies based on pluripotent stem cells.

Tino Sorge MdB

Making better use of Germany’s potential

And then, of course, there’s the US. The National Institutes of Health (NIH) alone have lately been spending more than $1.5 billion (€1.37 billion) per year on stem cell research. The wide range of funding schemes, strong capital base of universities and substantial investments made by the individual federal states have created an extremely favorable climate for stem cell research and regenerative medicine in the US over the last few years. In New York State alone, annual investments in stem cell research exceed the DFG’s total annual budget for basic stem cell research projects for the whole of Germany.

Based on their comparative analysis of the funding situation in the different countries, the authors of the GSCN white paper arrived at the following recommendations for political decision-makers and funding bodies: • Stem cell research as a cross-cutting discipline needs to move back up the research and innovation policy agenda. • In view of the increasing volume of public funding provided in other countries, Germany should draw level and invest more in stem cell research funding, also in the long term. • Funding needs to achieve a balanced mix of solid basic research and translational research. This combination is particularly well established in Germany and should continue to be closely linked in the future. • Funding formats to bridge gaps along the translation and value chain best address the needs of the diverse research landscape. Alongside centers and clusters, transregional and interdisciplinary research alliances are the ideal way of increasing the connectivity of the stem cell research community.

Berlin-Brandenburg Center for Regenerative Therapies BCRT

The Berlin-Brandenburg Center for Regenerative Therapies (BCRT) is an interdisciplinary translational center with the goal of enhancing endogenous regeneration by cells, biomaterials, and factors which can be used to develop and implement innovative therapies and products. At the BCRT clinicians and researchers are working closely together on a personalized medicine that depends on the early recognition of patients‘ individual healing potential. The primary focus of the BCRT is on diseases of the immune system, the musculoskeletal system, 30

the cardiovascular system and the kidney for which currently only unsatisfactory treatment options are available. Early cooperation with industry, health insurers and regulatory authorities as well as other external partners boosts the chances of exploiting new methods and provides access to flexible financing options. BCRT · Charité – Universitätsmedizin Berlin Augustenburger Platz 1 · 13353 Berlin www.b-crt.de


RESEARCH FUNDING

Moderator Ira Herrmann

The GSCN white paper was presented on 28 Sept. 2016, in the Habel am Reichstag restaurant to a group of parliamentarians and ministerial and public officials. The lunch-time event was rounded off with a discussion on the current state and future of stem cell research in Germany.

Findings of the White Paper are being presented by (from left) Daniel Besser, Barbara Ludwig, Albrecht Müller and Ulrich Martin. Ira Herrmann moderates.

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Mouse embryonic stem cells differentiated into neuroectoderm cells using embryoid bodies. Fluorescence staining shows neuronal marker β3Tubulin.

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RESEARCH AND APPLICATION

New national and international projects

Future perspectives in stem cell research A mix of powerful technologies has turned stem cells into a key tool for the life sciences both in basic research and clinical application. The huge diversity of innovation potential found in German labs is reflected in the joint research projects backed by the new BMBF funding initiative for stem cell technology. Collaboration between academic research and the pharmaceutical industry is also picking up tangibly, particularly for cell-based disease modeling and drug screening. This article presents a selection of new national and international projects and centers that are set to shape stem cell research over the coming years.

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bout ten years ago, Shinya Yamanaka revolutionized biomedical research with the discovery of human induced pluripotent stem cells (iPS cells). The technology was quickly adopted in German labs, too, and was soon followed by further developments such as genome editing with designer nucleases including TALENs and CRISPR-Cas9. The ability to create three-dimensional mini-organs called organoids and the mass production of differentiated cells have opened new horizons. In combination with new imaging techniques and bioinformatic analysis tools, research has advanced into areas that would have been unthinkable just a few years ago.

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Photos: HelmholtzZentrum Munich / Stefan Weiss, MPI Münster / Sabrina Desbordes

New joint research projects for innovative stem cell technology

The only way to preserve live cells for long periods is to store them at extremely low temperatures, normally provided by liquid nitrogen. This involves enzymatic removal of the cells from the supportive growth surface and freezing them as individual cell suspensions with cyroprotectants. However, this is always accompanied by the formation of ice crystals. “A considerable amount of cell function and even whole cells are lost in this process,” says Ina Meiser, head of the IBMT working group Cryobiotechnology. To get around this problem, the team of researchers is working on developing an innovative disposable plastic container in which all the necessary cell culture steps can be carried out and the cells cryopreserved without ice crystal formation. According to Meiser, this is especially useful for neuronal cells with their delicate dendrites that depend on adherent growth. Another advantage is that, after thawing, there is no need for the previously required recovery and cultivation phases, meaning that the cells are immediately available for experiments. “The iPS cells remain in the disposable container throughout, and can grow on the cell-specific surfaces and differentiate there as well,” says Meiser. Neural stem cells from iPS cells

The many different joint research projects supported by the new funding initiative of the Federal Ministry of Education and Research (BMBF) demonstrate the huge innovation potential of these procedures. The BMBF funding initiative “Innovative stem cell technologies in individualized medicine” established in 2015 is the first initiative for many years targeted specifically at stem cell researchers in Germany. The coordinating agency for the project, Germany’s aeronautics and space research center DLR, reported that the response was huge, with more than 70 research alliances submitting project proposals. Thirteen projects have been selected and will be funded with a total of €21 million up to 2020. A research alliance consists of two to five partners. All the projects funded aim to develop better cell-based disease models for research and test systems for drug screening.

Improving cryopreservation

The research alliance Stabil-Ice consists of a team from the Fraunhofer Institute for Biomedical Engineering (IBMT) in Sulzbach, south-west Germany, and neuroscientists from the University of Erlangen-Nuremberg who are aiming to make a significant improvement in the cryopreservation of iPS cells and the neuronal cells derived from them.


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Differentiation strategies for different types of neuronal cells are delivered by project partner Beate Winner from the University Hospital of Erlangen. Winner’s working group specializes in iPS cells derived from the fibroblasts of Parkinson’s patients.

Meiser reports that the first results from the ready-to-use system are already very promising. She is convinced that the stable ice system can make an important contribution to providing a supply of human nerve cells cost-efficiently and with a consistent level of quality. Demand for standardized cell material is especially high in the fields of drug development and testing, particularly for innovative therapies to treat neurodegenerative diseases. The BMBF is funding the project until the end of 2019 with around €950,000.

Kidney organ-on-a-chip for drug tests

Combining modern microsystem technology with organoids derived from iPS cells is the objective of the research alliance micro-iPS-Profiler. The four partners of the alliance are from Jena, Berlin and Heidelberg. They started work in November last year to develop a microfluidic chip on which an organ can be replicated and modeled in miniature format. The technology platform is being developed by a team headed by Holger Becker from Microfluidic ChipShop GmbH in Jena. For now, the researchers are focusing on the kidney for their organ chip. “The kidney is made up of many different cell types that we can already produce from pluripotent stem cells,” says Andreas Kurtz from Berlin Charité University Hospital. His team will deliver cell material from patients with kidney diseases. The challenge is to combine the cells into a functioning three-dimensional mini-organ, called an organoid. The

targeted outcome of the project is a multi-organ chip in which kidney and liver organoids are interconnected. The system could be used for high-throughput screening and testing of drugs. The BMBF is funding the project with €2.5 million. Meanwhile, the project partners in the PancChip alliance will be focusing on producing a pancreas chip for diabetes research. The team, headed by Heiko Lickert from the Helmholtz-Center in Munich and Matthias Meier from Freiburg will derive insulin-producing beta cells from stem cells and use them to construct the pancreas organoids. These three-dimensional model systems will be used by biomedical researchers to investigate the development of diabetes and possible replacement therapies in miniature format (funding: €1.5 million).

Bavarian Research Network Induced Pluripotent Stem Cells (ForIPS) Uniklinik Erlangen

ForIPS aims to establish the iPS technology and to use iPS cell derived neural cells as models to analyze the pathogenesis of Parkinson’s disease (PD). Scientists of ForIPS re-program skin cells from PD patients and healthy control subjects, and differentiate those patient specific iPS cells into neural cells. As these neural cells constitute very specific cellular models researchers hope to decipher the underlying pathogenic mechanisms of PD. 34

The core project is the heart of the Bavarian Research Network ForIPS. This platform provides human iPSCs and neuronal derivates from Parkinson patients and healthy controls. Scientifically, the core project aims to establish complementary nonintegrating reprogramming strategies. Another aim of the core project is to establish a biobank for human iPSCs in Bavaria. Setting up this efficient platform will be a starting point for advanced investigation of other brain diseases or disorders of other organs.

for more information please refer to www.bayfor.org/forips



serve as a translation center that combines modern stem cell technology with pharmaceutical research. It will use iPS cells and in vitro disease models for high-throughput drug testing. The State of Bavaria is providing €25 million of start-up financing for the center. The CARE concept was initiated by stem cell researcher Hans Schöler, head of the Max Planck Institute for Molecular Biomedicine in Münster. In his presentation of CARE to politicians, business representatives and scientists in April 2016, he said that the institute would employ around 60 members of staff. The center will initially focus on neurodegenerative, cardiovascular and rare diseases. Not just large, but also small and medium-sized enterprises operating in drug research will have the opportunity to actively engage in the center. CARE is to be built on the biotech campus in Martinsried.

Photo: Fotolia.de (JCG)

Translation: connecting academic research with the pharmaceutical industry Stem cell-based drug screening and drug development are becoming increasingly important in pharmaceutical research. The stem cell technology center CARE is being set up in Munich to facilitate progress in this field. CARE, the Center for Advanced Regenerative Engineering, will

The designated CARE managing director, Ulrich Gerth, has informed us that the contractual framework conditions are in the final agreement stage and the legal corporate structures are being prepared. The Dortmund-based Lead Discovery Center (LDC) is already an important partner of CARE. LDC is a translation company founded by Max Planck Innovation in 2008 and will be providing its expertise in the testing and validation of small molecules and chemical substances. The CARE coordinators in Munich are currently still exploring whether the LDC concept can be applied to the development and validation of biopharmaceutical agents.

Institute of Reconstructive Neurobiology From disease modeling to stem cell therapies The Institute of Reconstructive Neurobiology at the University of Bonn Medical Centre focuses on the use of pluripotent stem cells for the study and treatment of neurological disorders.

Based on a broad technology portfolio including cell reprogramming, neural differentiation, direct cell fate conversion, stem cell industrialization and neurotransplantation, the Institute develops stem cell-based model systems for disease-related research and drug development as well as novel cell therapy regimens. It closely Annual GSCN Magazine 2016/17

interacts with LIFE & BRAIN GmbH, a translational hub of the University of Bonn providing stem cell products and services for pharma, biotech and academia. Institute of Reconstructive Neurobiology LIFE & BRAIN Center University of Bonn Sigmund-Freud-Straße 25 · 53105 Bonn www.stemcells.uni-bonn.de

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Vitrification of hiPSC They grow in colonies and have cell-cell contact as well as cell-surface contact that need to be maintained. Living cells (Fluorescein Diacetate, green), dead cells (Ethidiumbromid, red)

After vitrification

New analgesic drugs to treat neuropathic pain An alliance of academic research and industry started up last year in North-Rhine Westphalia to investigate stem cell-based approaches to research on analgesic drugs. The consortium, called NeuRoWeg, is led by pharmaceutical company Grünenthal, and successfully secured a grant of €1.5 million in the first round of the leading market competition LifeSciences.NRW. The other partners in the interdisciplinary consortium are the Institute of Reconstructive Neurobiology at the University of Bonn, translation company LIFE & BRAIN GmbH and the University Hospital Cologne.

The research network will be investigating neuropathic pain. This pain is caused by disorders to the peripheral nervous system as a result of accident or severe disease. Using the example of diabetes-induced neuropathic pain, the NeuRoWeg researchers want to establish a stem cellbased system for basic research on pain and industrial drug research. Nerve cells of the pain system can be derived in the lab using iPS technology. The expertise in

After vitrification on thermal unstable material

the generation of pluripotent stem cells and their differentiation will be supplied by the research team from the Institute for Reconstructive Neurobiology headed by Oliver Brüstle. LIFE & BRAIN GmbH will be in charge of the standardized and automated mass production of cells and the development of informative test systems.

There was more good news in store for the Bonn-based stem cell researchers in December 2016. In the second round of the leading market competition LifeSciences. NRW, the consortium StemCellFactory III was selected for funding, thus securing the financing for the third phase of this flagship project. Over the last few years, a robotics line has been constructed on the premises of LIFE & BRAIN GmbH, with the support of the federal state of North-Rhine Westphalia, where iPS cells can be produced and matured into neural cells in a fully automated process. In the new round of funding, the research partners want to investigate standardized and integrated procedures for the individualized stem cell-based prediction of drug efficiency using reprogrammed blood cells.

Photo: Fraunhofer IBMT / Ina Meiser

Non-cryopreserved control

Fraunhofer Institute for Cell Therapy and Immunology IZI Fraunhofer IZI

The Fraunhofer Institute for Cell Therapy and Immunology IZI investigates and develops solutions to specific problems at the interfaces of medicine, life sciences and engineering. One of the institute’s main tasks is to conduct contract research for companies, hospitals, diagnostic laboratories and research institutes operating in the field of biotechnology, pharmaceuticals and medical engineering. The Fraunhofer IZI develops, optimizes and validates methods, materials and products for the business units Drugs, Cell Therapy, Diagnostics 36

and Biobanks. Its areas of competence lie in cell biology, immunology, drug biochemistry, bioanalytics and bioproduction as well as process development and automation. In these areas, research specifically focusses on the indications oncology, ischaemia, autoimmune and inflammatory diseases as well as infectious diseases and regenerative medicine. The institute works in close cooperation with hospital institutions and performs quality tests besides carrying out the GMP-compliant manufacture of clinical test samples. Furthermore, it helps partners obtain manufacturing licenses and permits.

Fraunhofer Institute for Cell Therapy and Immunology IZI Perlickstr. 3 · 04103 Leipzig www.izi.fraunhofer.de



EU consortium on iPS cells for replacement tissue and biobanks It’s all happening for German stem cell researchers at the European level as well, although the EU research project TECHNOBEAT has little to do with electronic dance. The eight partners from industry and research involved in the joint project TECHNOBEAT are exploring ways of making diseased hearts beat more strongly again using cultivated replacement cells. Tools and TECHNOlogies for Breakthrough in hEArt Therapies, in short TECHNOBEAT, has secured total funding of €6 million from the EU research and innovation program Horizon 2020. The coordinator of the international research consortium is stem cell researcher Robert Zweigerdt from the Medical School Hannover (MHH), with Eppendorf AG as the partner from industry. In the course of the next four years, the team of TECHNOBEAT researchers, medical experts and engineers will be devel-

AMSBIO is a long-established supplier of high quality tools and technologies to support stem cell research. Our extensive product portfolio supports every facet of stem cell research ranging from stem cell sources, iPSC reprogramming agents, and ready-to-use feeder cells to advanced xeno-free culture medium components and GMP grade cryopreservation media. Together with a comprehensive range of stem cell characterization products, differentiation reagents, and unique assay platforms AMSBIO is proud to offer the industry’s largest selection of 2D and 3D natural and recombinant extracellular matrices, including Cultrex BME 2 organoid growth matrix to enable the development of long-term (>1 year) organoid cultures. Annual GSCN Magazine 2016/17

oping effective tools and methods to create small pieces of heart tissue from human iPS cells. Engineers from Eppendorf subsidiary DASGIP Information and Process GmbH will be developing bioreactors for the mass reproduction and cultivation of iPS cells. The outcome will be three-dimensional cell aggregates of heart muscle cells that can be used to create replacement tissue for heart attack patients. The Innovative Medicines Initiative (IMI) has been a considerable factor in accelerating the take-up of stem cells as tools in the biomedical labs in research and industry. The IMI is a public private partnership of the European Commission and the EU pharmaceutical industry association EFPIA. Established in 2014 and coordinated by pharmaceuticals group Pfizer, the consortium EBiSC is working on producing well-characterized iPS cell lines and systematically archiving them in a non-commercial biobank. The joint project involving 27 partners (including seven from

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The technological potential of modern stem cell research raises new ethical and legal issues. What changes will the production of artificial germline cells using iPS technology bring to reproductive medicine? Can the developments coming from stem cell labs be patented? What are the problems involved in the clinical application of iPS cells? Under its funding priority “Ethical, Legal and Social Aspects of Modern Life Sciences and Biotechnology” (ELSA), the BMBF is funding six interdisciplinary research projects on the topic of stem cells. More information: www.gesundheitsforschung-bmbf.de/de/6620

Germany) with funding of €55 million has already borne the first fruits. In spring 2016 its online catalog from which researchers from academia and industry can request specific cell lines went live. Alongside the central EBiSC bio bank in Cambridge, UK, a mirror bank will be established at the Fraunhofer IBMT in Sulzbach, southwest Germany, as a full counterpart to the UK bank.

Max Planck Center of Regenerative Biomedicine opens in China The high degree of collaboration in the field of stem cell technology also extends far beyond the borders of Europe. As part of its internationalization strategy, the Max Planck Society has set up a new Max Planck Center in the Chinese city of Guangzhou, which was inaugurated in December 2016. The Max Planck – GIBH Joint Center for Regenerative Biomedicine brings together top researchers from two Max Planck Institutes and the Guangzhou Institutes of Biomedicine and Health (GIBH) of the Chinese Academy of Sciences. The new Max Planck Center is dedicated to using iPS technology to develop brain, cardiac and lung cells for the advancement of regenerative medicine and drug research. It is the first Max Planck Center to open in China and pools the scientific exper-

StemBANCC, an IMI consortium funded with €55 million, will be entering the home stretch in 2017. The consortium, which is coordinated by Swiss pharmaceuticals group Roche, consists of 35 partners, nine of whom are from Germany. StemBANCC is aiming to derive 1,500 iPS cell lines from 500 patients. They will be made available for future drug tests and disease models and will also be stored in the EBiSC bio bank.

Photo: MPI Münster

Spotlight on ethical and legal aspects

Fraunhofer Institute for Production Technology (IPT) Innovative solutions for stem cell research and production As a production engineering research institute, the Fraunhofer IPT offers many years of inhouse experience in production processes, metrological systems, process automation and quality management. In cooperation with researchers from academia and industry, we use our know-how to develop technical systems for quality control, handling and processing stem cells. The fields of application range from manufacturing and research on structured surfaces for the guided differentiation through mechanotransduction to fully automated 38

platforms and processes for the adaptive production of stem cells. This way we develop innovative and tailored solutions together with our partners and customers.

Fraunhofer Institute for Production Technology IPT Steinbachstr. 17 · 52074 Aachen www.ipt.fraunhofer.de/LSE



Joint projects on stem cell technology funded by the BMBF The BMBF is funding 13 research alliances and 49 subprojects in total. The projects announced so far are:

tise of Max Planck directors Hans Schöler from Münster, Thomas Braun and Werner Seeger (both from the Max Planck Institute for Heart and Lung Research in Bad Nauheim) and Duanqing Pei from GIBH, which is affiliated to the Chinese Academy of Sciences, and its Hong Kong laboratory group. As you can see, there are plenty of good ideas and exciting collaborative projects going on in the stem cell research community in Germany. The GSCN will be supporting these promising activities with its work in the coming years.

Text: Philipp Graf

Micro-iPS-Profiler MAIV – Modeling of ALS in vitro Stabil-Ice Models of the blood-brain barrier for drug development in Alzheimer’s disease PancChip – Pancreas development and disease models on an iPSC chip platform PDdementia – Cellular iPS models correlated to clinical settings to identify drugs counteracting the cognitive decline in the finale stages of Parkinson’s Neuro2D3 – Standardized model systems for late onset neurological diseases and drug screening in 2D and 3D cultures StemNet iPStemRNA More information: www.gesundheitsforschung-bmbf.de/de/6753.php

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Differentiated neurons made from iPS cells of a schizophrenia patient; staining of SOX2 (nucleus, red) and TBR1 (cytoplasm, green) and DNA staining in blue.

stem cell bank

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REGENERATIVE MEDICINE

Regenerative medicine

Testing clinical maturity While stem cell therapies have become standard in the treatment of leukemia, it will take a good few years until pluripotent stem cells can be used as a resource in regenerative medicine. The first clinical trials with replacement tissue developed from pluripotent stem cells have started around the world. But how safe and how effective are these new therapies? The stem cell community wants to harmonize standards for producing clinical-grade cells from pluripotent stem cells and is testing the quality of the cells to optimize their clinical application. Systematic online catalogs such as hPSCreg are an important resource here. The GSCN working group Clinical Trials brings together stem cell experts and regulatory authorities to address important issues in good time.

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hile stem cells have become a fixed component of drug research and drug development, the clinical application of cell-based therapies is still largely confined to the experimental stage. Cell-based therapies are highly complex and generally tailored to individual patients. They are also subject to stringent regulatory requirements and manufacturing standards. As with other drugs, stem cell-based therapies have to be tested for their safety and effectiveness in clinical trials (cf. GSCN Annual Magazine 2015/2016). The register of clinical trials clinicaltrials.gov has registered more than 2,000 stem cellbased studies, the majority of which are related to hematopoietic stem cells and mesenchymal stem cells (MSCs).

Photo: Uni Halle / Matthias Jung; MDC / David Ausserhofer

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A new generation of cell replacement therapies is emerging across the world and also throughout Europe. A number of clinical trials of preparations based on human embryonic stem cells (ES cells) and induced pluripotent stem cells (iPS cells) are already underway. “At present, 30 clinical trials are taking place around the world based on pluripotent stem cells, mostly ES cells,” says Andreas Kurtz of the Berlin-Brandenburg Center for Regenerative Therapies (BCRT) at the Charité. He is one of the initiators of the GSCN’s strategic working group Clinical Trials and Regulatory Affairs.

cell replacement therapies for heart tissue that has been damaged by heart attacks and replacement therapies with dopamine-producing neurons for Parkinson’s patients. The R&D work is, however, taking place in partnerships outside of Germany – in Toronto, New York and Boston. “Stem cell-based therapy developments in Germany have not yet reached sufficient maturity to be available as partners for these kinds of initiatives from the pharmaceutical industry,” says Daniel Besser from the GSCN Central Office. “We need to strengthen structures here in the country to facilitate the translation of our excellent basic research into application.”

Stem cell register hPSCReg has its sights on clinical application

The pluripotent cell lines used by the Bayer start-up may also one day be recorded in the stem cell register hPSCreg.eu.

Charité researcher Andreas Kurtz is one of the coordinators of hPSCreg, further partners are the Barcelona stem cell bank at CMR[B], the UK Stem Cell Bank near London and the Chinese Academy of Sciences. The online information portal was launched in 2007 with a grant from the European Commission to create transparency in the use by research labs of the controversial ES cells. The unprecedented success of iPS technology in the production of pluripotent stem cells has caused a rapid increase in the number of en-

Bayer banking on cell therapies

Just how important the latest generation of regenerative therapies is in the eyes of the big pharmaceutical companies became clear in December last year when the Bayer group created a stir by founding the start-up BlueRock Therapeutics. Together with venture capital fund Versant Venture, Bayer is investing the gigantic sum of $225 million in the start-up to develop highly efficient therapies based on iPS cells. BlueRock Therapeutics will initially focus on


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tries in the register. The portal has expanded its range of functions accordingly and subjects the registered cells to in-depth testing according to clearly defined standards. “We are now the leading global register for pluripotent stem cell lines,” says Kurtz. In February 2017, the register included 690 ES cell lines and 452 iPS cell lines. The records for each cell line include information on their origin, their molecular biological profile, their scope of application and, of course, their storage location.

information standards together with international partners from Japan, the United Kingdom and the United States. These are uniform data formats designed to help improve information exchange between cell banks and registers.

iPS cell banks linking up

In Japan, a study involving the world’s first iPS cell-based therapy to treat a retinal disease. has been resumed. The trial had been put on hold as a precautionary measure after genetic mutations were discovered in the cells to be transplanted to a patient suffering from macular degeneration.

Fraunhofer Institute for Molecular Biology and applied Ecology IME The Fraunhofer IME conducts research in applied life sciences from a molecular level to entire ecosystems. Our interdisciplinary organization and laboratories with most recent equipment including GMP facilities and complex facilities for environmental simulations allow a wide spectrum of research and development services. IME’s overarching goal is the development and use of novel technologies for diagnosis and therapy of human and animal disease as well as protection of crop plants and food supplies. IME has close ties in terms of personnel and areas of work with 42

Photos: MDC / Norman Krüger, MDC / David Ausserhofer

The European Commission plans to continue funding the hPSCreg at least for the next four years. “We will now focus in particular on cell lines that are suitable for clinical application,” says Kurtz. The most important task now is to further develop and harmonize the required quality standards. “We want to become an international platform for harmonization,” says Kurtz. Plans are also afoot for hPSCreg to record and present all future clinical trials that are conducted worldwide on the basis of pluripotent stem cells. Kurtz and his five-strong bioinformatics team have also developed minimum

IME

the Institute of Molecular Biotechnology of the RWTH Aachen University, the Department of Biology and Biotechnology of Plants of the University Münster, the Department of Applied Entomology of the University Gießen and the Institute for Clinical Pharmacology of the Goethe University Frankfurt/Main. Fraunhofer IME Forckenbeckstraße 6 · 52074 Aachen

Fraunhofer IME ScreeningPort Schnackenburgallee 114 · 22525 Hamburg www.ime.fraunhofer.de



Pluripotency staining of an induced pluripotent cell line, stained with surface marker SSEA4, pluripotency factor SOX2 and DAPI nuclear staining

The study team led by Masayo Takahashi from Kobe adapted their strategy and are now using allogeneic cells instead. These cells are derived not from the patients themselves but from donors whose cells are genetically flawless and as immunologically compatible with the patient as possible.

The concept works in the same way as the immunological donor selection for stem cell transplantations. The cells used are ideally derived from persons with blood type 0 and who are homozygous for a characteristic tissue-compatibility antigen pattern – so-called haplotypes of the HLA system.

Many experts regard the storage of such immune-matched iPS cells in biobanks as key for the regenerative medicine

of the future. However, only a globally connected initiative will be able to ensure that suitable cells can be found for a given patient. The Global Alliance for iPSC Therapy (GAiT) represents a step in this direction. This collaborative project of various institutes including the New York Stem Cell Foundation and UK’s Cell Therapy Catapult aims to set up iPS haplo banks with cells that are quality assured as clinical grade. Here too, Andreas Kurtz and his Berlin bioinformatics team are making an important contribution: “We are building a database for the GAiT to record the cell lines. We want to set standards here and push for their application. And in the medium term we hope to become a resource for the regulatory authorities, too.”

As a spin-off from the Medical Faculty, Heinrich-Heine- University Düsseldorf and the Max Planck Institute for Molecular Biomedicine Münster, RheinCell Therapeutics company focuses on the GMP compliant production of human induced, pluripotent stem cells (iPSC) from HLAhomozygous cord blood stem cells. GMP compliant episomal reprogramming technologies are employed to develop a mastercellbank of HLA-homozygous iPSC, which can be used as ATM-products for a variety of allogeneic off the shelf transplantations, e.g. retina pigment epithelial cells for the treatment of macula degeneration or CAR-T/NK-cells for the treatment of solid tumors.

RheinCell Therapeutics GmbH · Berghausener Straße 98 · D-40764 Langenfeld


www.rheincell.de

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Centralized service units with clinical relevance

well and has also attracted attention abroad. The stem cell core facility in the Dutch city of Leiden has also recently joined the network.

The contacts created through the network have already proven useful for the joint acquisition of third party funding. The Federal Ministry of Education and Research is funding a three-year joint project called iPStemRNA that has partners from Munich, Berlin, Bergisch Gladbach and Dresden. The project is dedicated to developing iPS cell lines that meet the stringent requirements of good manufacturing practice, or GMP. This is a prerequisite for their use in future cellular therapies. Furthermore, these iPS cell lines are to provide an immune-compatible match for the majority of the population at the level of the major tissue-compatibility antigens (HLA). Micha Drukker from the Institute for Stem Cell Research at the Helmholtz Zentrum München is the project coordinator. Further participants

Photos: MDC / David Ausserhofer

Infrastructure is being built up in Germany to pave the way for pluripotent stem cells from bench to bedside. In the last few years, several large research institutes in Germany have set up centralized service units for pluripotent stem research, known as stem cell core facilities (cf. GSCN Annual Magazine 2014/2015). With the assistance of the GSCN and the Berlin Institute of Health (BIH), the PluriCore network was set up two years ago. This network is a joint initiative of the stem cell core facilities of Aachen, Berlin, Bonn, Dresden, Erlangen, Freiburg, Göttingen, Hamburg, Hannover, Kiel, Münster and Munich that aims to establish common standards for experiments and to promote the sharing of experience and material. The concept is working

Institute for Stem Cell Research and Regenerative Medicine (ISRM) Regenerative Medicine at a glance

At the institute for stem cell research and regenerative medicine we adopt a systems biology approach to better understand normal development (hepatogenesis, nephrogenesis and neurogenesis), ageing and disease mechanisms (Steatosis/Non Alcoholic Fatty Liver Disease, Alzheimer’s Disease, Nijmegen Breakage Syndrome and Crigler-Najjar syndrome). We are actively involved in the EU/FP7 funded project AgedBrainSYSBIO (http://agedbrainsysbio.eu/) where we study mechanisms underlying late onset Alzheimer’s Disease (LOAD).Mechanisms underlying the induction and maintenance of pluripotency and the derivation of patient speci44

fic induced pluripotent stem cells (iPSCs) differentiated into relevant cells types (2D and 3D) are core to these efforts. Omics-based datasets (transcriptome, proteome, methylome and secretome) Bioinformatics, mathematically modeling, pathway reconstruction and data management are central to our research. Heinrich-Heine-Universität Universitätsklinikum Düsseldorf · ISRM Moorenstr. 5 · Geb. 14.80.01.002 · 40225 Düsseldorf www.uniklinik-duesseldorf.de/ISRM



are the cell therapy center TUMCells (Martin Hildebrandt, Munich), Sebastian Diecke from BIH Stem Cell Core in the Max Delbrück Center for Molecular Medicine (MDC) and the team of Dresden-based transfusion expert Thorsten Tonn. The industry partner for the project is Miltenyi Biotec GmbH from Bergisch Gladbach. The BMBF is funding the joint research project with just under €1.5 million.

The GSCN working group Clinical Trials collaborates closely with the Paul Ehrlich Institute (PEI), Germany’s federal licensing authority for biomedical drugs. One example of this collaboration is a joint workshop that was held on 10 Nov. 2016 in Langen. As it is hoped that clinical trials with iPS cell-based preparations will be starting in the next few years in Germany as well, the GSCN wants to elaborate joint positions with the PEI for next-generation cellular therapies and regenerative medicine. The joint initiative will also be addressing further topics such as mesenchymal stem cells, the ethical aspects of licensing, and the manufacturing permits of the federal states. Text: Philipp Graf

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career

public affairs

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disease modelling

organoids


public outreach

perspectives

ethical aspects

clinical studies

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genetic engineering

stem cell banks

CAREER DEVELOPMENT

Career development

Well-equipped for a career A wide range of professional opportunities both in science and in private enterprise is open to stem cell researchers once they have obtained their doctorate or post-doc qualification. The GSCN Career Development group aims to help young scientists find the right career path by offering special sessions at the GSCN annual conferences as well as multi-day workshops. The working group also places a special focus on careers for women in stem cell research and is currently considering setting up a support scheme for young families.

W

hy are stem cell researchers in such high demand on the labor market? For Insa Schröder, a researcher based in Darmstadt, one reason immediately springs to mind. “The special thing about us is that we are used to working in highly interdisciplinary teams,” she says, “but we need to communicate this advantage more clearly to industry.” Schröder, a certified food chemist, herself embodies this diversity: after several stints working in toxicological and biomedical research in Berlin, Washington and Halle/Leipzig, she took up a position at the Helmholtz center for heavy-ion research (the GSI Helmholtzzentrum für Schwerionenforschung) in Darmstadt. Here she is conducting research into the impact of radiotherapy on tissue regeneration. “There are all kinds of different career paths to choose from, which makes things exciting but not always easy,” says Schröder. “We want to help young scientists actively shape their careers.”

s

ks

Photo: GSCN

The strengths of stem cell researchers

Schröder initiated the GSCN strategic working group on Career Development together with Hartmut Geiger, head of the Institute of Molecular Medicine at Ulm University. For Geiger, a researcher on aging processes in stem cells, it is his passion for his field of research that motivates him to engage in career development work: “If we want to attract more people to this fascinating field of research we need to offer mentoring services, and I’m happy to take an active role here.” He points out that the interdisciplinary mindset of stem cell researchers is not their only advantage. “Stem cell research often tends to be extremely complex. It takes special skills to truly understand the topics involved.” A further strength of the research area is its translational component, i.e. the application-oriented connection to clinical work and pharmaceutical research. “This makes stem cell researchers very innovative and flexibly deployable,” says Geiger. The German Stem Cell Network’s career development activities are based on three pillars: The GSCN annual confer-


ence, with around 400 participants last year, has become a highlight for young stem cell researchers from the bachelor to senior post-doc level. Geiger believes this annual meeting is an ideal platform for young scientists here in Germany. “There’s lots of interaction at the conference and it offers all kinds of networking opportunities. This gives young researchers a good feel for their position in the field and the options ahead.”

For the GSCN annual conferences, Schröder and Geiger organize a special session on career development. “We don’t just have people talking about their career in academic research or in the pharmaceutical industry,” says Insa Schröder. It is important to her that the guest speakers also always present alternative career paths – in other words, the world of work beyond the stem cell laboratory. There are, after all, interesting careers awaiting stem cell researchers in patenting, media, specialist publishers and science communication.

Workshops for scientists in executive positions

Once a year, the GSCN holds a multi-day workshop for the smaller target group of young scientists aiming for academic leadership positions. The workshop is not just relevant to experienced post-docs: “Anyone who does a PhD will end up in a leadership position at some point – and they need to be prepared for that,” says Schröder. The workshop-style course is held by a professional coach for ten to twenty participants. The last intensive course focused on a topic of nothing less than existential importance: How do I write a funding application for my own position? Many people are not aware of the diversity of funding options available to stem cell researchers, says Schröder.

Nonetheless, it is clear that stem cell researchers aiming for an academic career in Germany will be confronted with harsh realities. The situation has become especially difficult in the university environment. Public research institutes offer very few permanent positions for scientists other than professorships. “The mid-level faculty structures are still very underdeveloped,” says Schröder with regret. “Permanent positions for lab managers for example are urgently needed,” she adds. Most of the positions are externally financed with third-party funds and the institutions themselves are having to cope with ever tighter budgets. This means that most posts are temporary. To make the system more flexible again, experts are calling for more permanent positions that are, however, regularly subjected to quality controls and adapted accordingly.

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CAREER DEVELOPMENT

More tenure track professorships on the horizon The good news is that the federal government intends to improve the prospects of young academics. The Federal Ministry of Education and Research (BMBF) is launching its tenure track program in 2017. This will see the federation investing one billion euros in a pact with the federal states to set up 1,000 additional tenure track professorships at universities. Geiger and Schröder regard this is as a long overdue step in the right direction. The “new” Excellence Initiative, agreed on last year, is also set to give fresh momentum to the research landscape across Germany from 2019. This time round, the strategy includes a separate funding line for smaller universities and technical colleges called “Innovative Hochschule”. The 2013 National Report on Junior Scholars, BuWIN 2013, shows that eighteen months after completing their PhD, 44 percent of bioscientists are still working in research (31 percent at universities, 13 percent at non-university research institutes), while 29 percent are in the public sector and 27 percent in private enterprise. There is a definite trend towards private enterprise, which is hardly surprising as it offers good payment, permanent positions and promising career development opportunities. Many people are not actually aware of the diversity of jobs open to them. Alongside pharmaceutical companies, there are also interesting career prospects in the biotech industry. The annual corporate survey by web portal biotechnologie.de revealed that in 2015 around half of the 600-odd German biotech com-

panies operate in Insa Schröder (left) and Hartmut Geiger (re), the medical here with Frank Emmrich, organize workshops sector, covering a for the promotion of young scientists broad spectrum of fields from drug development to diagnostics. Clinical research organizations (CROs) that conduct clinical trials on behalf of pharmaceutical developers also have attractive positions for qualified stem cell researchers.

Taking a broader view and grasping opportunities

Anke Raloff from academics.de, a career portal that provides extensive information for scientists looking for a job as well as running the online job market of the newspaper Die Zeit, advises graduates to think about career paths outside academia at an early stage. “Many career starters only look at their academic qualifications and the requirements stipulated by companies in their job descriptions.”

Raloff’s expert advice for young professionals is rather to rely on their own strengths and skills and to broaden their view of the options open to them. She advises jobseekers to “look at the opportunities outside of their narrow qualification tunnel” and have the courage to apply for positions

Heidelberg Institute for Stem Cell Technology and Experimental Medicine HI-STEM gGmbH

HI-STEM gGmbH is a non-profit public-private partnership between the German Cancer Research Center (DKFZ) and the Dietmar Hopp Foundation (DHS).

Located within the DKFZ in Heidelberg, HI-STEM performs cutting-edge research on stem cells with the aim of translating these results into novel clinical applications. This includes the development of novel diagnostic tools and innovative therapies to monitor and target leukemic and solid tumor stem cells as well as metastatic disease. 48

Professor Dr. Andreas Trumpp and four Junior Group Leaders direct an international research team of more than fifty employees.

The HI-STEM Research Groups: • Hematopoietic and Leukemic Stem Cells (A. Trumpp) • Experimental Hematology (M. Milsom) • Stress induced activation of HSCs (M. Essers) • Cancer Stem Cells and Metastasis (A. Trumpp & M. Spick) • Metastatic Niches (T. Oskarsson)

HI-STEM gGmbH German Cancer Research Center (DKFZ) Im Neuenheimer Feld 280 · 69120 Heidelberg www.hi-stem.de


CAREER DEVELOPMENT

even if they are not an exact fit to their professional qualifications. She says it is also well worth going to job fairs and talking to companies there directly. And, of course, the young professionals should also come to the GSCN annual conferences, where the industry exhibition includes precisely those companies most relevant to stem cell researchers.

While preparing her lectures offering extensive tips on job applications, such as the one she gave at the 2016 GSCN Annual Conference in Hannover, Raloff often browses the Internet looking for inspiration from corporate websites with good career pages of their own. “Companies that have a dedicated section for job applicants and that provide a lot of information show how important it is to them to recruit top talent.”

Photo: GSCN

Better work-life balance and more family time

Even though the air definitely gets thinner in the higher ranks of academic research, Insa Schröder remains optimistic. “In my experience, if someone is passionate about their work, they will find a way.” Nonetheless, embarking on a career in research requires a certain degree of flexibility and mobility.

This stands in stark contrast to the expectations of the current generation of students who want more job security and, increasingly, a better work-life balance. Fortunately, things

have changed in this respect at the research institutes, says the Ulm-based biomedical expert Geiger: “The days when your prospects for promotion went hand in hand with the number of hours you spent in the lab are over.” A bit more nous is what’s required to tackle today’s complex tasks successfully and you can switch that on at home, too. Another priority issue for the GSCN is to focus more on the careers of women working in stem cell research. The Female Scientist Award, a special prize awarded by the GSCN at its annual conference each year, is an example of the network’s efforts in this area. The proportion of female researchers working in leading positions in science and private enterprise is still very low. Insa Schröder sees the award as sending a very powerful message. “The award-winners are role models that show how successful women can be in top-level research.” Hartmut Geiger also emphasizes how important diversity is for the German research landscape and for the GSCN.

Supporting young researchers is not just about helping them choose their career paths and preparing them for their chosen careers. Many doctoral students and postdocs are also first-time parents or already have more than one child. The Career Development working group also wants to address this issue. The GSCN is currently considering setting up a financial support scheme to make it easier for young families to combine childrearing with their research work and help them to maintain the momentum in their careers. Text: Philipp Graf

The Collaborative Research Center SFB 873 Maintenance and differentiation of stem cells The Collaborative Research Center SFB 873 “Maintenance and Differentiation of Stem Cells in Development and Disease” at Heidelberg University works towards defining the regulatory principles underlying the balance between maintenance, expansion and differentiation of stem cells in diverse systems on a mechanistic level. To this end the SFB873 studies a wide spectrum of experimental models ranging from plants to human to elucidate the inherent properties of specific stem cell systems, but also to uncover common and divergent principles behind regulatory regimes and molecular signaAnnual GSCN Magazine 2016/17

tures. Our consortium brings together internationally recognized researchers, with unique scientific strengths in cell biology, biophysics, developmental biology, molecular medicine or modeling. With our research we hope to advance our understanding of principles underlying stem cell function and lay the foundation for translational approaches. Centre for Organismal Studies (COS) Im Neuenheimer Feld 230 · 69120 Heidelberg www.sfb873.de

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UniStem Day 2016

PUBLIC OUTREACH

Stem cells – learning opportunities for everyone

Advancing awareness and understanding: GSCN public outreach work On 11 March 2016, groups of school students flocked to scientific institutions in eight German cities, researchers kitted themselves out with nametags and steeled their nerves, and heart surgeons explained to the youngsters how stem cells can be used to treat cardiac disease. It was all part of a major campaign that gave 1,000 high school students children across Germany the chance to spend the day learning about stem cells. The GSCN’s public outreach work aims to present stem cell research in a simple and intelligible way to all interested parties. It uses a wide variety of different tools and methods to do so, including lectures, one-to-one conversations, videos, interactive games, lab tours, handson experiments, exhibitions, flyers and articles, and is constantly adding creative new formats to the list. Students in Hannover were even allowed to watch a lung transplant as part of the public outreach campaign, all in the name of raising awareness and interest in stem cell research and to enable people to form well-founded opinions on the issues concerned. Science communicators are always on the search for new ideas to get particular groups interested in this rapidly advancing field.

I

Photos: GSCN

n spring 2016, the target group were high school students taking part in Germany’s first UniStem Day. The German Stem Cell Network and participating institutes had spent one year organizing and planning this event to make it a success. UniStem Day is the first centrally organized educational day in Germany dedicated purely to stem cell research. The goal of the event was for exhausted and fascinated students to go home in the evening with an understanding of the potential of stem cells, the significance of their versatility, and what cell reprogramming is all about. They would have grasped why research is not the same as treatment, why research often seems to take so long, how to become a researcher and why it is so important that ethics, reflection and social debate accompany developments in stem cell research. These kinds of public outreach activities are designed to introduce young people, future researchers and future patients and their relatives to the fascination and also the realities of research at a very early stage. The GSCN has set itself the task of advancing awareness and understanding of stem cells within society. It aims to present the complex web of scientific findings, the associated ethical implications and the long developmental path towards translation, clinical trials and treatments in a way that is


understandable to the general public and to decision-makers. This also means that stem cell researchers must be prepared to listen to the fears and concerns of diverse civic groups and individuals and explain the facts in formats such as panel discussions and interviews. “I recently took part in a discussion on stem cell research with theologians and Catholic business people and it proved to be extremely interesting and enriching for both sides,” says GSCN managing director Daniel Besser, who appreciates opportunities to discuss the subject with groups traditionally situated at the opposite end of the spectrum. “Stem cell research is a very complicated field so we cannot expect everybody to immediately understand the material and the implications involved.” For the GSCN, it is therefore important that its public outreach activities include many different formats that match the level of knowledge and communication styles of all the various target groups in question, from students to patients and the elderly. “We tend to find that elderly people are particularly interested in our public events and specially designed series of exhibitions on stem cells and disease,” explains Besser. Short videos on stem cell researchers and their work are shown at the GSCN events to give participants an easily understandable introduction to the debate. It is absolutely essential to stick to the facts. The GSCN takes care not to exaggerate the achievements of the research or play down or ignore the associated risks. “It is very important to us not to stir any unfounded fears or raise unfounded hopes,” says Besser.

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PUBLIC OUTREACH

“A lot of journalists and patients called us up at the institute asking about stem cells, iPS cells and the opportunities and risks involved,” says Tobias Cantz. He was working at the Max Planck Institute for Molecular Biomedicine in Münster at the time, in the laboratory of Hans Schöler, the researcher at the center of the attention in 2006. “As a physician, I am experienced in telling patients carefully but clearly about their medical situation and their treatment options. I transferred this attitude to the way I approached the general public.” In Münster, one of the hotspots of the debate on stem cell research, biomedical scientists and ethic experts set up a website on stem cell research in partnership with the Protestant Church. It is called Zellux and is targeted at schoolteachers and school students. “We wanted to create a website that provides validated high-quality information on the subject. The internet was awash with so much unverified information at the time, some of which was completely unfounded and absurd. So we wrote all of the information and teaching material for the site ourselves.” Since then, Tobias Cantz has been not just a researcher but also passionately involved

52

“One of the first target groups of our public outreach work were politicians,” says Ira Herrmann, coordinator of the GSCN working group on public outreach together with Tobias Cantz, reflecting on her time as managing director of the competence network for stem cell research of NorthRhine Westphalia. Following Prof. Oliver Brüstle’s application to use embryonic stem cells for research purposes in 2002, she was inundated with inquiries on the topic. She focused her public relations work on politicians and the press but also served the information needs of interested members of the general public. The research findings reported on by the media soon sparked the interest of another group, namely patients. “They called us desperately wanting treatment that we were obviously not able to provide. It’s sometimes difficult to offer objective advice in such cases,” says Ira Herrmann. She came up with a new approach to help remedy this situation, initiating a lecture as part of further training measures for family physicians to inform them about the opportunities and risks of stem cell therapies. “We were thus able to reach out to the disseminators who are the first point of contact in healthcare matters and are often in direct contact with people with chronic illnesses over many years,” says Hermann. In the first few years Hermann provided patients directly with information in English from Canada and the US before she created a German website on the subject together with the competence network team. In 2016, she summarized the facts and questions on non-validated therapies and important aspects for patients in a flyer on behalf of the GSCN. This gives patients answers to their most pressing concerns and puts them in a position to ask the right questions themselves, for example of providers of stem cell therapies.

Photos: Uni Bonn / GSCN

The need to improve public understanding and for effective science communication became apparent when stem cell research first came into the public eye in a big way. The media attention generated by a stem cell researcher’s application to use human embryonic stem cells for research purposes in 2002 and the discovery of iPS cells in 2006 sent the demand for information and debate through the roof.

in public outreach work. Even after ten years of experience working with school classes and teachers, the young professor still takes a keen interest in observing and contributing to the development of students’ attitudes and arguments. “I consider this is a really important part of my work. It gives me the chance to hear the opinions of the younger generations and I particularly enjoy talking with them about ethical principles.” His work with young people keeps Cantz curious. And he has noticed that the vehemence of the public debate on stem cell research has declined and been replaced by a more practical take on ethics. Asked about his wishes for the future, he says that he would like to provide students with even better information so that they can better understand and discuss the dynamics, the potential and also the ethical issues involved in recent developments in biomedicine. To achieve this and also to counter knowledge gaps in the future, Cantz is currently serving as expert advisor for the teaching material being developed for schools in Germany by the German Stem Cell Network and the Ernst Schering Foundation. The material will be available from May 2017 on the website www.stammzellen-verstehen.de


PUBLIC OUTREACH

The German Stem Cell Network has engaged in a variety of new activities since 2013, including public panel discussions and films on German stem cell researchers and their work, all of which are designed to encourage the interested public to think about stem cells. “We have been able in the meantime to develop a range of tried and tested methods to reach as many groups as possible,” says Daniel Besser. The biggest campaign so far was UniStem Day, and the most recent effort is to create up-to-date teaching material for four teaching modules, presented to students in the form of a conference. The network is now setting its sights on creating a film portal with GSCN-produced researcher portraits, like the ones in the United Kingdom that have made it onto the bestseller click list of the European outreach network EuroStemCell. Text: Stefanie Mahler

German Stem Cell Network public outreach material – www.gscn.org: • Teaching material for high-school students; www.stammzellenverstehen.de; www.diskurslernen.de; www.zellux.net • Education material for highschool www.stammzellen-verstehen.de • GSCN films on stem cell researchers and their work • Comics • Games: organ game, cell differentiation game, card game • Poster exhibition with quiz • Flyer about online portals providing validated information on stem cells • GSCN annual magazine with detailed insights into the research landscape

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53

GSCN ANNUAL REPORT

GSCN Annual Report Boards

Executive Board In accordance with Section 8(1) of the statute and rules of the German Stem Cell Network (GSCN) e.V., the Executive Board (presidium) consists of the Active President* (chairperson), the Senior President (first vice chair), the Designated President (second vice chair), the Treasurer, and the Assessor. In the reporting period (Sept. 2016 – Sept. 2017), the Executive Board is made up of the following members: Active President (Chair)

Prof. K. Lenhard Rudolph (Leibniz Institute on Aging – Fritz Lipmann Institute [FLI], Jena) [email protected]

Senior President (first vice chair)

Prof. Ulrich Martin (Hannover Medical School) [email protected]

Designated President (second vice chair)

Prof. Ana Martin-Villalba (German Cancer Research Center Heidelberg) [email protected]

Treasurer

Dr. Michael Cross (Leipzig University) [email protected]

Assessor

Prof. Frank Emmrich (Fraunhofer IZI, Leipzig) [email protected]

The Executive Board in 2016

The newly elected executive board for 2017 (from left): Michael Cross, K. Lenhard Rudolph, Ana Martin-Villalba as future president, Uli Martin and Frank Emmrich.

54

The GSCN would like to thank the members of the 2016 Executive Board (Sept. 2015 – Sept. 2016). Thomas Braun, Active President in 2015, left the Executive Board as scheduled and is still involved in the GSCN as a highly valued advisor and initiator of the working group “Somatic stem cells and development.”


GSCN ANNUAL REPORT

Extended Board In accordance with Section 9(1) of the statute and rules of the GSCN e.V., the Extended Board consists of up to 15 persons. In the reporting period, the Extended Board is made up of the following members: Prof. Oliver Brüstle (University of Bonn) [email protected]

Dr. Tobias Cantz PD (Hannover Medical School) [email protected]

Dr. Micha Drukker (Helmholtz Zentrum München) [email protected]

Prof. Frank Edenhofer (University of Innsbruck) [email protected]

Prof. Hartmut Geiger (Ulm University) [email protected]

Prof. Magdalena Götz (LMU Munich) [email protected]

Ira Herrmann (Life & Brain) [email protected]

Prof. Albrecht Müller (University of Würzburg) [email protected]

Prof. Dr. Michael Rieger (Goethe University Frankfurt) [email protected]

Prof. Ingo Roeder (TU Dresden) [email protected]

Prof. Hans R. Schöler (Max Planck Institute for Molecular Biomedicine Münster) [email protected]

Prof. Andreas Trumpp (German Cancer Research Center Heidelberg) [email protected]

Prof. Mathias Treier (Max Delbrück Center for Molecular Medicine Berlin) [email protected]

Prof. Wolfgang Wagner (RWTH Aachen) [email protected]

Prof. Claudia Waskow (TU Dresden) [email protected]


55

GSCN ANNUAL REPORT

Working group initiators Scientific working groups Pluripotency and Reprogramming

Somatic Stem Cells and Development

Basic, Translational and Applied Hematopoiesis Stem Cells in Diseases (Cancer Stem Cells) Stem Cells in Regenerative Therapies Stem Cells in Disease Modeling and Drug Development

Computational Stem Cell Biology

Strategic working groups Funding Programs and Policies

Career Development

Public Engagement and Outreach Activities Patient Information (Stem Cell Therapies) Clinical Trials and Regulatory Affairs

Stem Cell Technologies

56

Dr. Micha Drukker Prof. Hans Schöler Prof. Mathias Treier

Prof. Thomas Braun [email protected] Prof. Federico Calegari (CRTD Dresden) [email protected] Prof. Ana Martin-Villalba Prof. Elly Tanaka (IMP Vienna) [email protected] Prof. Claudia Waskow Prof. Timm Schroeder (ETH Zürich) [email protected]

Prof. Thomas Brabletz (University Medical Center Freiburg) [email protected] Prof. Andreas Trumpp Prof. Ulrich Martin Prof. Wolfgang Wagner

Prof. Oliver Brüstle Prof. Karl-Ludwig Laugwitz (University Hospital Klinikum rechts der Isar, Munich) [email protected] Prof. Georg Füllen (Institute for Biostatistics and Informatics in Medicine and Ageing Research Rostock) [email protected] Prof. Ingo Röder Prof. Ulrich Martin Prof. Albrecht Müller Active GSCN President (ex-officio)

Prof. Hartmut Geiger (Ulm University) Prof. Jürgen Hescheler (University Hospital Cologne) [email protected] Dr. Insa Schröder (GSI Helmholtz Centre for Heavy Ion Research) [email protected] Dr. Tobias Cantz PD Ira Herrmann

Dr. Gisela Badura-Lotter (Ulm University) [email protected] Ira Herrmann

Dr. Andreas Kurtz (BCRT Berlin) [email protected] Prof. Torsten Tonn (Institute for Transfusion Medicine Dresden) [email protected] Prof. Hans-Dieter Volk (BCRT Berlin) [email protected] Dr. Zoltán Ivics (Paul-Ehrlich-Institut Langen) [email protected] Dr. Andreas Bosio (Miltenyi GmbH, Bergisch Gladbach) [email protected] Prof. Frank Emmrich


GSCN ANNUAL REPORT

Facts and figures Meetings

Executive Board meetings

The Executive Board of the GSCN regularly holds meetings and telephone conferences. These meetings are coordinated and organized by the Central Office. The following Executive Board meetings took place in 2016: • Video conference, 17 June 2016 • Meeting, 11 and 12 Sept. 2016 in Hannover • Meeting, 1 Dec. 2016 in Frankfurt am Main

Extended Board meetings

• 12 Sept. 2016 in Hannover • 1 Dec. 2016 in Frankfurt am Main

General Assembly

• 12 Sept 2016 in Hannover

Overview of members in 2016 Total no. of members Individuals Legal entities

397 Full members

222

Students

146

Research institutes

17

Companies with more than 20 full-time staff

5

Companies with fewer than 20 full-time staff

6

Partner societies

1

Membership cancelations in 2016

16

Members of the working groups Scientific working groups

Pluripotency and reprograming

203

Somatic stem cells and development

157

Basic, translational and applied hematopoiesis Stem cells in diseases (cancer stem cells)

153

Stem cells in disease modeling and drug development

165

Stem cells in regenerative therapies

218

Computational stem cell biology Strategic working groups


38

Funding programs and policies

142

Career development

127

Clinical trials and regulatory affairs

109

Public engagement and outreach activities

66

Patient information (stem cell therapies)

23

Stem cell technologies

79

206 Last updated 31.12.2016

57

GSCN ANNUAL REPORT

Institute members

Company members

• Berlin-Brandenburg Center for Regenerative Therapies (BCRT) • Center for Regenerative Therapies Dresden (CRTD) • German Cancer Research Center (DKFZ), Heidelberg • ForIPS Bavarian Research Network at the Universitätsklinikum Erlangen • Fraunhofer Institute for Molecular Biology and Applied Ecology (IME), Aachen • Fraunhofer Institute for Production Technology (IPT), Aachen • Fraunhofer Institute for Cell Therapy and Immunology (Fraunhofer IZI), Leipzig • Institute of Reconstructive Neurobiology, University of Bonn • Institute for Stem Cell Research and Regenerative Medicine, Düsseldorf • Leibniz Institute on Aging – Fritz Lipmann Institute (FLI), Jena • Leibniz Institute for Zoo and Wildlife Research in the Forschungsverbund Berlin • Max Delbrück Center for Molecular Medicine (MDC), Berlin-Buch • Max Planck Institute for Heart and Lung Research (MPI-HLR), Bad Nauheim • Max Planck Institute for Molecular Genetics (MPIMG), Berlin • REBIRTH Cluster of Excellence, Hannover Medical School (HMS) • Collaborative Research Center SFB 873, Centre for Organismal Studies, Heidelberg University Hospital • Tissue Engineering and Regenerative Medicine (TERM), University Hospital of Würzburg

• AMS Biotechnology (Europe) Ltd. • Biological Industries • Eppendorf AG • HI-STEM gGmbH • MacoPharma Int. GmbH • Miltenyi Biotec (from 2017) • PELOBiotech GmbH • PeproTech GmbH • RheinCell Therapeutics GmbH • Takara Bio Europe SAS • Thermo Fisher Scientific – LSG

Partner societies • German Society for Transfusion Medicine and Immune Hematology (DGTI)

GSCN General Assembly

GSCN members vote at the members meeting in Hannover 58

Photo: GSCN

Ninety-one members attended the fourth General Assembly of the GSCN, held on 12 Sept. 2016 during the 4th Annual Conference in Hannover. The minutes of the assembly and the presentation that formed part of it can be downloaded from the members’ area of the website. The Executive Board and the Extended Board were re-elected in the online elections of August 2016 (see above), after the auditors officially discharged the previous board members.


GSCN ANNUAL REPORT

Activities in 2016

In 2016 the GSCN tried out new ways of engaging with the public and consolidating its role as a network. The public outreach working group of the GSCN initiated and organized a new national stem cell day for senior high-school students. Regarding public affairs, the GSCN presented political decision-makers with an analysis of public funding for stem cell research triggering much-needed discussion on the issue. In its capacity as a network, the GSCN initiated new formats and stepped up its participation in international conferences and international networking workshops.

The network

The GSCN Annual Conference is the largest and most important meeting of stem cell researchers in Germany. Around 400 scientists gathered at the 4th GSCN Annual Conference held at the Hannover Medical School. The conference provided ample opportunity for scientific exchange and to spark new plans and cooperations. A new and original aspect was the Networking Evening in the zoo: glorious summer temperatures and great design of the zoo provided the perfect setting to forge contacts, discover professional and personal commonalities, and make new friends. Personal networks play an important role in the initiation and success of current and future projects. In the follow-up to the conference, participants extensively addressed the topic of trouble shooting at the Non-PI Meeting in Hannover (15 Sept. 2016), a GSCN format that has become an established and much appreciated event.

On an international level, the GSCN brought people together at the ISSCR Annual Meeting in San Francisco (22 – 24 June 2016) with its second WunderBar Evening. The event, held in a brewery, was attended by around 95 guests and was deemed a great success. The traditional GSCN Meet-Up Hub took place in the exhibition area of the ISSCR Meeting and attracted many German and international GSCN


members and their colleagues who valued the opportunity for intensive exchange in the middle of the conference. Among them were the six junior scientists who had won the chance to cross the big pond to the ISSCR courtesy of the GSCN Travel Awards granted by the GSCN working groups. The travel award recipients were: Avni Baser (Heidelberg), Cristina Golfieri (Dresden), Stefan Hauser (Tübingen), Chao Sheng (Bonn), Manuela Völkner (Dresden), and Stefan Weiss (Munich). They were all extremely impressed by the inspiring atmosphere of the big international conference, the diversity of the sessions and the academic qualify of the lectures as well as the presence of renowned international figures in stem cell research. Networking means forging contacts that can help advance one’s work and professional career. The GSCN Awards are awarded by the GSCN as a means of promoting promising careers and motivating other young researchers. In 2016 the GSCN awarded three prizes endowed with €1,500 and the chance to give a lecture at the central Presidential Symposium at the GSCN Annual Conference: • The GSCN 2016 Young Investigator Award went to Dr. Leo Kurian from the Center for Molecular Medicine Cologne (CMMC) of the University of Cologne. • The GSCN 2016 Female Scientist Award went to Prof. Claudia Waskow from the TU Dresden.

• The GSCN 2016 Publication of the Year Award went to Dr. Guangqi Song, Dr. Martin Pacher, Prof. Michael Ott and Dr. Amar Deep Sharma from the REBIRTH Center and TwinCore at the Hannover Medical School for the publication “Direct Reprogramming of Hepatic Myofibroblasts into Hepatocytes In Vivo Attenuates Liver Fibrosis“ in the journal Cell Stem Cell (Song, G. et al., 2016, Cell Stem Cell, 18, 797 – 808, doi: 10.1016/j.stem.2016 .01.010.).

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GSCN ANNUAL REPORT

The GSCN also takes part in, supports and organizes workshops, sessions and seminars with other organizations to foster its contacts on a scientific, administrative and collegial level: The GSCN was Silver Supporter of the ISSCR Meeting in Dresden (1 – 3 Feb. 2016) providing scientific and financial support as well as organizing the session on “3D Cultures & Organoids”. At the IGDL Meeting in Hamburg (25 – 27 Feb. 2016) the GSCN was patron of a satellite symposium on deepening “special knowledge”. At the PluriCore-Meeting in Berlin (19 – 20 May 2016), supported by the GSCN, core facility staff from across Germany met to share new protocols and ideas. “We are extremely grateful to the GSCN for its generous financial, logistical and scientific support,” said Sebastian Diecke at the opening of the meeting. At the annual conference of the DGTI in Nuremburg (7 – 10 Sept. 2016), the GSCN organized a satellite symposium with Thomas Brabletz, Robert Zweigerdt, Susanne Kleber and Gerald Schumann. In 2016, the GSCN supported the following events: • StemCellMathLab Workshop (16 – 18 June) in Hamburg

• 3rd Conference on Cell Therapy Manufacturing and Testing (2 – 3 Nov.) in London, UK

• Workshop on Computational Tools for Single-Cell Transcriptomics (14 ov.) in the Helmholtz Zentrum München

• 2nd Challenges in Computational Biology: Gene Expression Analysis Conference (1 – 2 Dec.) with a satellite student Symposium on Computational Genomics (30 Nov.) in Mainz

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A GSCN PEI Workshop (10 Nov. 2016) in Langen was dedicated to regulatory matters regarding the development and clinical application of pluripotent stem cells. The strategic working group Career Development organized a two-day further training course “How to write a successful grant application to support yourself” for 12 junior investigators in Ulm (24 – 25 Nov. 2016). The workshop was booked out very quickly and was rated as extremely helpful in the feedback. “We hope that all the participants will be able to put what they learned to use in the near future and be successful in their applications. Watch out reviewers, from now on all applications for stem cell research will be perfectly worded!” said event organizer Hartmut Geiger on the course and outcome of the workshop.

The GSCN also took another important step with its evaluation by the implementing agency VDI-TZ. At the milestone meeting on 3 June 2016, VDI-TZ attested that the GSCN conducts outstanding work and has delivered on all parts of the project. This includes building up the network, attracting members and growing membership, organizing a range of events (conference, satellite symposia, workshops), setting up working groups, providing information and performing public outreach work.

In 2016, the GSCN again granted Travel Awards to enable talented junior scientists to take part in various conferences and summer/winter schools. Thanks to these awards, Birte Baudis (Cologne), Christian Böhme (Leipzig), Larisa Condurat (Freiburg), Nora Freyer (Berlin), Devy Garna (London) and Florian Murke (Essen) were able to attend the GSCN Annual Conference in Hannover. All Travel Awards were funded by GSCN company member Eppendorf AG. Also in 2016, the GSCN granted Travel Awards to Jerome Korzelius, Jena, to attend the Gordon Research Conference: Tissue Niches & Resident Stem Cells in Adult Epithelia in Hong Kong; Goveas Neha, Dresden, for the Hydra XII Summer School; Marisa Karow, Munich, to go to the Annual Meeting of the Society of Neuroscience in San Diego; Nancy Mah, Berlin, for the 2nd Challenges in Computational Biology Gene Expression Analysis Conference in Mainz and Miriam Hetzel, Hannover, for the ISSCR/ESGCT International Symposium in Florence.


GSCN ANNUAL REPORT

Workshop „Train the trainer“ for European science communicators in Berlin, organized by EuroStemCell and the GSCN

Communication A network is based on communication and the exchange of information – both on a scientific and a personal level in the working groups, at the conference, and in the workshops and committees. There were two particularly striking highlights in the GSCN’s communication activities this year. First, the GSCN published its white paper “Public funding of stem cell research – Germany in international comparison” presenting it to a group of German Bundestag politicians and public officials in Berlin on 28 Sept. 2016. The paper’s analysis between the US, the UK, Sweden, Japan and Germany showed that while public funding for stem cell research has been declining in Germany, it has rising steadily in the other countries investigated where the cross-cutting technology is regarded as a driver of innovation. The objective of the GSCN white paper is to persuade politicians to step up their political and financial support for stem cell research to enable Germany to maintain its leading global position in this field. A new highlight of the GSCN in 2016 was the first UniStem Day. The GSCN organized an educational day for school students across the whole of Germany. On 11 March 2016 approximately 1000 school students in eight cities flocked to a total of 17 research institutes to spend the day learning all about stem cell research through games, films, lab tours, lectures, speeches, expert consultations and company tours. The feedback from the institutes, researchers, teachers and students was extremely positive. Not only German school students spent the day learning about stem cell biology – a total of 27,000 school students across Europe dedicated the day to learning about stem cells. The UniStem Day was also the topic of a project presentation given by


Stefanie Mahler at the forum on scientific communication, Forum Wissenschaftskommunikation, in Bielefeld (5 – 7 Dec. 2016). The UniStem Day also showed how constructive and successful the work of the GSCN Communication on Stem Cell Research group has been in getting the participating institutes involved. School students were the target audience of the GSCN events at the debate on stem cells and ethics at Haus Kreisau youth education center (28 Jan. 2016) and at the MINT400 Forum in Berlin in Adlershof (4 – 5 Feb. 2016). For students wanting to learn more about new professional fields, Daniel Besser offered tours around the campus as part of international seminars (29 Feb. and 2 March 2016) and discussed stem cell research with young US scientists in the program of the Council on International Educational Exchange (CIEE).

Internationally, the GSCN collaborates closely with EuroStemCell. The two networks jointly organized the workshop “Train the Trainer 2” (31 Oct. – 1 Nov. 2016) in Berlin. The GSCN was the host for 25 international science communicators who spent two days exploring possible ways of communicating stem cell research. There was much discussion, sharing of experiences, projects, methods and materials and the participants learned a lot from one another. For the interested general public, the GSCN held a panel event in the follow-up to its Annual Conference in Hannover (14 Sept. 2016). Facilitator Stefanie Seltmann (DKFZ) and panel members Axel Haverich, Ulrich Martin, Michael Manns, Tobias Cantz (all from MHH) and Nils Hoppe (Leibniz Universität Hannover) debated the possibilities of stem cell therapies in treating heart and liver disease.

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GSCN ANNUAL REPORT

The latest GSCN films about Michael Manns and Tobias Cantz, Ulrich Martin and Nils Hoppe were also shown. These have now been translated into English and are also available on the GSCN website at: www.gscn.org/en/RESOURCES/GSCNMovies. aspx. Cultivating contacts within a network always also involves passing on information. The GSCN makes use of various communication channels. At the conference the annually updated mobile app “GSCN 2016” enabled participants to shape their visit to the conference to suit their personal interests. The GSCN also provides information and news in English and German on its website www.gscn.org. The website’s news column that spotlights international articles on the latest developments in the field is particularly popular. The GSCN films, job market and conference announcements also attract great interest. By email, the Central Office sends out the GSCN Newsletter, which focuses on different topics in each issue. In 2016, the GSCN published a new image brochure, the annual magazine 2015/16 (1,100 copies) and a patient flyer with information on the latest developments in stem cell therapies and questions that patients should ask before they opt for a particular treatment. The internal communication platform Humhub serves as a forum for all members and is used in particular by the Central

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Office to provide advance information on workshops, conferences and to call for applications for travel grants.

The GSCN is also active on social media including Facebook, LinkedIn and Twitter and has a growing number of followers. The GSCN Central Office regularly receives inquiries from teachers, students, patients and journalists, which are answered with the help of scientists. The GSCN conference, in particular, prompts nationwide coverage in print and online media.

Finances

The GSCN is a non-profit organization funded by membership subscriptions and grants from the BMBF. Under Section 4 of its statute, the level of subscriptions is set by rules adopted at the General Assembly. Subscriptions are detailed on the GSCN’s membership form. The business year is the calendar year. Subscriptions are due at the start of the business year. The Executive Board is responsible for producing the annual accounts and submitting them to the General Assembly. Details of the association’s finances are provided at the General Assemblies.


Photos: GSCN


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