Handbook of Experimental Pharmacology - Springer

Handbook of Experimental Pharmacology

Volume 174

Editor-in-Chief F. Hofmann, München Editorial Board J. Beavo, Seattle, WA D. Ganten, Berlin M. Michel, Amsterdam C. Page, London W. Rosenthal, Berlin

Anna M. Wobus

•

Kenneth R. Boheler

Editors

Stem Cells Contributors M.R. Alison, C. Badorff, N. Benvenisty, B. Berninger, N. Beyer Nardi, A. Branzi, M. Brittan, P. Budde, G.A. Colvin, H. Darr, C. Denning, S. Dimmeler, F. Dönmez, M.S. Dooner, R. Enseñat-Waser, L.J. Field, M. Götz, G. Grenier, M. Hack, R. Harris, J. Jones, T. León-Quinto, M. Lovell, C. Mummery, R. Passier, G. Paul, P.J. Quesenberry, J.A. Reig, E. Roche, S. Rose-John, M. Rubart, M.A. Rudnicki, H. Sauer, L. da Silva Meirelles, B. Soria, N.D. Theise, C. Ventura, M. Wartenberg, G. Weitzer, N.A. Wright

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Professor Anna M. Wobus, PhD In Vitro Differentiation Group Dept. of Cytogenetics Leibnitz Institute of Plant Genetics and Crop Plant Research (IPK) Corrensstr. 3 D-06466 Gatersleben Germany [email protected]

Kenneth R. Boheler, PhD Investigator Laboratory of Cardiovascular Science Gerontology Research Program National Institute on Aging, NIH 5600 Nathan Shock Drive Baltimore, MD 21224 USA [email protected]

ISBN: 978-3-540-77854-7 Handbook of Experimental Pharmacology ISSN 0171-2004 Library of Congress Control Number: 2008920054 c Springer-Verlag Berlin Heidelberg 2008


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Preface

Significant advances in stem cell research and their potentials for therapeutic applications have attracted the attention of the scientific community and captured the imagination of society as a whole. Not so long ago, the study of most stem cells, other than those that regenerated the haematopoietic system, was rather obscure and limited to a relatively small number of researchers and laboratories. The uproar over stem cells really began in 1998 with the successful derivation of pluripotent human embryonic stem (ES) cells by James Thomson and co-workers. This breakthrough and the subsequent generation of specialized human cells in vitro led to a paradigm shift within the scientific community, which transformed this specialized endeavour from a topic of scientific interest to a line of investigation with the potential to generate cells capable of treating serious ailments, including diabetes, cardiovascular diseases and neurodegenerative disorders. Thus the dawn of regenerative medicine has spawned from the somewhat esoteric study of stem cells. Since 1998, extensive research endeavours have been devoted to the study of both embryonic and adult stem cells. Early reports suggested that adult stem cells had a higher plasticity than previously believed, perhaps even comparable with that demonstrated by embryonic stem cells, but several observations of the so-called transdifferentiation capacity and plasticity of adult stem cells have not been repeated. These reports, however, encouraged on-going debates about the capacity of adult versus embryonic stem cells and their potential use in regenerative medicine. Although at times controversial, these research efforts led to a better, although still limited, understanding of stem cells with respect to their identification, isolation, and developmental capacities. Importantly, stem cells do not represent static entities that do not differ between embryos and adults. In fact, embryonic stem cells in early embryos represent basic units of life in higher organisms, while adult stem cells in somatic tissues represent cellular stores capable of regenerating tissue and maintaining organ functions. Regardless of these differences in potential, all stem cells derived from the embryo or adult are characterized by unique properties that permit accurate cell copying in vivo in a process termed selfrenewal. Additionally, all stem cells retain the capacity to differentiate into more mature cell types. It is the degree of self-renewal and differentiation potential that differs among the various stem cell populations and cell lines.

VI

Preface

These common traits have led to vigorous scientific and ethical debates, which are likely to persist for many years. Adding to the scientific and ethical dilemmas surrounding stem cells was the successful transfer of human somatic nuclei into fertilized human oocytes in a process known as nuclear transfer (nt), and the creation through a process known as therapeutic cloning of human ntES cell lines by South Korean scientists in 2004. This has recently (May 2005) been followed by the efficient generation of patient-derived ntES cell lines, which will likely influence the ethical debate and growth of stem cell research in the future. For the first time and as a consequence of these developments, stem cell research coupled with molecular biology and tissue engineering techniques constitute a potential basis for rational therapeutic strategies of regenerative medicine. Moreover, human ES-derived somatic cells may represent innovative pharmacological tools for drug screening, the identification of new drug targets and cell-based compound delivery systems. Finally, these cells may facilitate an unravelling of the hitherto inaccessible paradigms of human development. In 2004, during one of the most contentious periods of debate with respect to the scientific, ethical and legal issues of stem cell research, the Board of Editors at the Handbook of Experimental Pharmacology approached us to edit a special volume devoted to stem cells. The idea was attractive because it would give us the chance to solicit and combine in one volume a body of work encompassing the rapidly advancing developments of stem cell research with a state-of-the-art view of stem cell biology. We invited leading experts in the fields of embryonic and adult stem cells to submit chapters for this volume, and although it proved impossible for everyone to submit a manuscript within the designated time frame, this volume is a compilation of their and our efforts to assemble an overview of the important aspects and issues surrounding stem cell research. The first two chapters are dedicated to molecular mechanisms regulating self-renewal and differentiation of human (Darr and Benvenisty) and mouse (Weitzer) ES cells. In the latter, the author describes how ES cell research, through the in vitro use of the embryoid body model, reflects early developmental processes in vivo (Weitzer), and in the following contribution, Wartenberg et al. demonstrate how the in vitro model system can be employed for the study of angiogenesis and tumour-induced angiogenesis. The following chapters review the present state of knowledge with respect to mouse and human ES cell-derived cardiac (Rubart and Field; Passier et al.) and pancreatic (Roche et al.) cells and their potential application in tissue repair of heart diseases and diabetes, respectively. Ventura and Branzi describe autocrine and intracrine signalling pathways implicated in ES-derived cardiogenesis and how pharmacological approaches may facilitate this process. The subsequent chapters deal mainly, but not exclusively, with adult stem cells, and the authors discuss mechanisms and potential applications of these cells in regenerative medicine. A unique concept of stem cell regulation based on haematopoietic stem cells (Quesenberry et al.) and a detailed overview that

Preface

VII

reflects the importance of markers in adult tissue-based stem cells (Alison et al.) are the perfect introduction to this set of chapters. Next, the chapters describe how haematopoietic stem/progenitor cells (Rose-John) or mesenchymal stem cells (Beyer Nardi and da Silva Meirelles) isolated from bone marrow may be isolated and manipulated by ex vivo expansion for tissue regeneration. Neovascularization and cardiac repair by bone marrow-derived stem cells (Badorff and Dimmeler) and the use of different stem/progenitor cells for myogenic tissue repair (Grenier and Rudnicki) are the topics of the following contributions. Neural stem cells, their properties and implications for the treatment of neurodegenerative diseases are extensively described and critically discussed by Berninger, Hack and Götz. The experimental studies described in the special issue are then complemented by a detailed description of the present state of a stem cell therapy with respect to patients with Parkinson’s disease (Paul). To end this special volume, we have selected a chapter dedicated to the future of stem cell research. Theise and Harris present a stimulating discussion on how unexpected and controversial findings of adult stem cell research may open up new perspectives to foster our understanding of cell biology. We are deeply grateful to all the contributors for their active participation and significant contributions to this volume. We are aware that this volume could not and does not cover all topics and aspects of stem cell research. In fact, and during the past few years, stem cell research has metamorphosed into distinct and specialized avenues of research; however, we believe that this volume presents in a single book many novel aspects of stem cell biology with respect to scientific endeavours and future applications. Of particular note are the pharmacological issues that have been compiled, which have never been adequately addressed in the past. We also would like to thank Mrs. Susanne Dathe, desk editor biomedicine at Springer, and Mrs. Kathrin Seiffert, IPK Gatersleben, for their support and expert editorial help. In conclusion, we hope that this volume will be valued by researchers in the field, and by those who are engaged in the future developments of stem cell research and the applications of stem cells in regenerative medicine. Gatersleben, Germany, Baltimore, MD, May 2005

Anna M. Wobus Kenneth R. Boheler

List of Contents

Factors Involved in Self-Renewal and Pluripotency of Embryonic Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . H. Darr, N. Benvenisty

1

Embryonic Stem Cell-Derived Embryoid Bodies: An In Vitro Model of Eutherian Pregastrulation Development and Early Gastrulation . . . G. Weitzer

21

Embryonic Stem Cells: A Novel Tool for the Study of Antiangiogenesis and Tumor-Induced Angiogenesis . . . . . . . . . . . . . . . . . . . . . M. Wartenberg, F. Dönmez, P. Budde, H. Sauer

53

Cardiac Repair by Embryonic Stem-Derived Cells . . . . . . . . . . . . M. Rubart, L.J. Field

73

Cardiomyocytes from Human Embryonic Stem Cells . . . . . . . . . . 101 R. Passier, C. Denning, C. Mummery Autocrine and Intracrine Signaling for Cardiogenesis in Embryonic Stem Cells: A Clue for the Development of Novel Differentiating Agents . . . 123 C. Ventura, A. Branzi Therapeutic Potential of Stem Cells in Diabetes . . . . . . . . . . . . . 147 E. Roche, R. Enseñat-Waser, J.A. Reig, J. Jones, T. León-Quinto, B. Soria The Stem Cell Continuum: A New Model of Stem Cell Regulation . . . . 169 P.J. Quesenberry, G.A. Colvin, M.S. Dooner Markers of Adult Tissue-Based Stem Cells . . . . . . . . . . . . . . . . 185 M.R. Alison, M. Brittan, M.J. Lovell, N.A. Wright Designer Cytokines for Human Haematopoietic Progenitor Cell Expansion: Impact for Tissue Regeneration . . . . . . . . . . . . . . . . 229 S. Rose-John

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List of Contents

Mesenchymal Stem Cells: Isolation, In Vitro Expansion and Characterization . . . . . . . . . . . . . . . . . . . . . . . . . . . . 249 N. Beyer Nardi, L. da Silva Meirelles Neovascularization and Cardiac Repair by Bone Marrow-Derived Stem Cells . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 283 C. Badorff, S. Dimmeler The Potential Use of Myogenic Stem Cells in Regenerative Medicine . . 299 G. Grenier, M.A. Rudnicki Neural Stem Cells: On Where They Hide, in Which Disguise, and How We May Lure Them Out . . . . . . . . . . . . . . . . . . . . . . . . . . 319 B. Berninger, M.A. Hack, M. Götz Cell Transplantation for Patients with Parkinson’s Disease . . . . . . . . 361 G. Paul Postmodern Biology: (Adult) (Stem) Cells Are Plastic, Stochastic, Complex, and Uncertain . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 389 N.D. Theise, R. Harris Subject Index . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 409

List of Contributors Addresses given at the beginning of respective chapters

Alison, M.R.

185

Badorff, C. 283 Benvenisty, N. 1 Berninger, B. 319 Beyer Nardi, N. 249 Branzi, A. 123 Brittan, M. 185 Budde, P. 53 Colvin, G.A.

169

Field, L.J.

73

Götz, M. 319 Grenier, G. 299 Hack, M. 319 Harris, R. 389 Jones, J.

147

Mummery, C.

101

Passier, R. 101 Paul, G. 361 Quesenberry, P.J.

169

Reig, J.A. 147 Roche, E. 147 Rose-John, S. 229 Rubart, M. 73 Rudnicki, M.A. 299

Darr, H. 1 Denning, C. 101 Dimmeler, S. 283 Dönmez, F. 53 Dooner, M.S. 169 Enseñat-Waser, R.

León-Quinto, T. 147 Lovell, M. 185

147

Sauer, H. 53 Silva Meirelles, L. da Soria, B. 147 Theise, N.D. Ventura, C.

389 123

Wartenberg, M. 53 Weitzer, G. 21 Wright, N.A. 185

249