For all these reasons, fetal progenitor cells have been used for the production of ... same fetal progenitor cells as fe
THE DIFFERENCE IS IN DIFFERENTIATION: ELANIX PROGENITOR CELLS FOR TISSUE REGENERATION AND REPAIR
EXECUTIVE SUMMARY Progenitor cells are biological cells that
substance to the advantages of progenitor
share
cells enumerated at the outset. Section
characteristics
significantly
different
with, from
but
behave cells.
three examines the role of progenitor cells
This paper explores these differences and
stem
in tissue homeostasis and repair. Section
examines some of the arguments behind
four discusses the clinical precedents behind
Elanix Biotechnologies’ use of progenitor cells
Elanix’ technologies and provides information
for the development of products for tissue
about the biological bandages developed for
regeneration and repair, chief among which
the treatment of severe burn patients at
is their greater stability and predictability.
the Lausanne University Hospital (CHUV). In
After providing a cursory description of Elanix,
conclusion, section five briefly discusses the
the introduction describes some of the
direction in which Elanix is taking its product
advantages presented by progenitor cells for
development. Throughout this paper, the
tissue repair. Section two provides important
guiding thread is the advantage gained in
detail on the distinction between progenitor
using progenitor cells for tissue regeneration
cells and stem cells, and thus brings more
and accelerated wound healing solutions.
1.
Elanix Progenitor Cells
PROGENITOR CELLS FOR TISSUE REPAIR
Elanix Biotechnologies is a tissue
a general climate that tends to
more predictable, safer, and just as
regeneration company active in
give preference to stem cells in
effective. As will be discussed in more
the f ields of Advanced Wound
regenerative
research,
length in the following pages, fetal
Management and Advanced Skin
Elanix recognizes clear advantages to
progenitor cells have been observed
Care which aims to become an
the use of progenitor cells for targeted
to naturally initiate scarless healing
important player in the world of
indications. While progenitor cells
in
regenerative
core
have similar properties to stem cells
are exciting from a therapeutic
competence is the development of
and behave in a similar fashion,
perspective, and have fueled the
progenitor cell technology originating
they stand out mainly in their
biotechnological research of Elanix’
from and used for over 15 years
greater predictability, which makes
scientific team for several decades.
within the Burn Unit at the Lausanne
them easier to manipulate and
University
medicine.
Its
medicine
CHUV
work with in culture. In addition,
Universitaire
this also considerably reduces risks
Vaudois) in Lausanne, Switzerland.
related to undesirable or unplanned
The activities of Elanix Biotechnologies
differentiation. These considerations
are predicated upon the potential
explain the underlying rationale for
of
choosing progenitor cells as the basis
(Centre
Hospital Hospitalier
progenitor
regeneration
cells
or
for
products.
tissue Within
for
tissue
regeneration
the
womb.
These
properties
products:
2.
Elanix Progenitor Cells
DISTINGUISHING PROGENITOR CELLS FROM STEM CELLS
are still concerns regarding their Stem cell and progenitor cell terminology is often confusing
tumor-inducing
potential
once
in the literature because both terms are f requently used to
implanted in vivo. It is known that
describe adult stem cells. Progenitor cells, however, are not
in vitro differentiated stem cells can
stem cells! While it is true that stem cells and progenitor cells
significantly lack stability. They can
share some biological characteristics, they also differ in several
de-differentiate and, depending on
important ways:
their environment, start multiplying or differentiating into other unplanned cell
Embryonic stem cells, adult stem cells, and progenitor cells: Embryonic stem cells, commonly
such as bone marrow, placenta, skin
referred to simply as stem cells,
or adipose tissue (1, 2). The cells are
can be isolated from early stage
multipotent, meaning that they are
embryos (< 2 weeks). These are
able to differentiate into a number
undifferentiated,
that
of cell types (neurons, chondrocytes,
they do not represent any specif ic,
osteoblasts)(3,4,5) depending on the
specialized adult cell type. In other
factors present in their environment.
words, for example, they have not
Adult
yet committed to becoming liver,
advantages over embryonic stem
bone, or skin cells. They have
cells: tissue for cell isolation can
high self-renewal and proliferation
easily be obtained, higher numbers
capacities
totipotent,
of stem cells are isolated from a
meaning they can differentiate into
single tissue biopsy, and thus in vitro
any
a
culture conditions are significantly
new organism in vivo. While the
less demanding and less costly.
potential of in vitro engineered
These properties are highly attractive
product
where the goal is to create in vitro
this
type
and of
meaning
are
cell
and
development
unlimited
form
is
high,
differentiation
stem
biological
cells
structures
have
to
risk
of adult stem cells have long and
teratoma
formation, a kind of tumor.
tumorous
replace
damaged tissues. Certain varieties
with
including
several
capacity is also the basis for the associated
types,
formations (6).
successful records of clinical use, such as the bone marrow transplant,
Adult stem cells can be identified
which have been performed for
and isolated from different tissues
over
40
years.
However,
there
3.
Elanix Progenitor Cells
Progenitor cells are early descendants of stem cells. Progenitor cell reservoirs are found in many adult tissues such as the brain, blood system, skin, or intestine (7,8) where they participate in tissue homeostasis and tissue repair (9). They can also be ethically isolated from human fetuses between 9 and 14 weeks in the eventuality of a voluntary interruption of a pregnancy. In contrast to stem cells, progenitor cells do not self-renew and are highly restricted in their differentiation (10,7,11,12). This means that specific progenitor cells will only develop into their intended cell types and do not present the same unpredictability as stem cells. This is of major importance to the safety of their usage in biotechnology as it significantly reduces the risk of tumor formation. Overall, progenitor cells are stable, easy to handle in culture, and their high proliferation potential allows the generation of cell banks for biological applications (10,13,14). For all these reasons, fetal progenitor cells have been used for the production of different vaccines for decades such as the polio vaccine, and research is ongoing to use the same fetal progenitor cells as feeder cells for keratinocyte expansion in the treatment of burn patients (15,16).
One donation
Bone cells Skin cells
Tendon cells
Cartilage cells
Muscles cells
Disque cells
4.
Elanix Progenitor Cells
THE ROLE OF PROGENITOR CELLS IN TISSUE HOMEOSTASIS AND REPAIR
The underlying biological mechanisms
seen, for example, in chronic wounds
differentiating
to
replenish
the
of tissue homeostasis and repair are
that never manage to fully heal and
cellular pool on an ongoing basis.
complex processes which are not
pose significant health risks in the
yet fully understood. We do know
long- term.
Two main mechanisms of action
however that both stem cells and
have been proposed for stem cells
progenitor cells are involved and play
This description of the body’s natural
a key role in ensuring the successful
response to the trauma of a new
outcome of this natural process.
wound demonstrates how important
A)
the stem and progenitor cells are
homeostasis,
Upon injury, the tissue repair system
in the healing process. One of the
proliferate and terminally differentiate
is readily activated and involves the
initiators and part of the coagulation
to produce new tissue (9,12,17,18).
very precise coordination of multiple
cascade are platelets, which serve as
cell types to successfully heal tissue.
reservoirs releasing all kinds of factors
B) adult stem cells and progenitor
This is well observed in wound
that attract and influence these cells.
cells help tissue recovery through
healing where the body’s response
and progenitor cells in tissue repair. in
order
paracrine
to
maintain
progenitor
activity:
tissue cells
endothelial
starts in a matter of seconds after
Consider, for example, the case of
progenitor cells have been shown to
the wound with the activation of the
tissues with a high cell turnover
secrete angiogenic growth factors
coagulation cascade to stop blood
such as skin, intestine, or blood. The
which induce neovascularization, fetal
loss, followed by the recruitment of
lifespan of keratinocytes and red
progenitor cells have been shown to
immune cells to clear pathogens
blood cells is only 30 days and 120
improve adipose-derived stem cell
and cellular debris, the activation of
days, respectively. As a result, these
growth in co-culture experiments,
skin cells for reepithelization which
tissues must constantly be renewed
and amniotic epithelial cells produce
leads, in turn, into the process of scar
to maintain tissue homeostasis and
exosomes that stimulate fibroblast
maturation. Improper coordination
functionality. Progenitor cells present
proliferation and migration in vitro
between the different cell types or
in these tissues provide this function
(19,20,21,22).
stages results in inefficient repair as
by
multiplying
and
terminally
5.
Elanix Progenitor Cells
CLINICAL PRECEDENTS: PROGENITOR FETAL CELL EXTRACTS FOR WOUND HEALING SOLUTIONS
During
their
early
gestational
development, from the appearance of fetal progenitor cells until week 24, fetuses have the ability to heal
Before treatment
skin wounds rapidly and without scarring. This particularity is not due to the uterus environment but rather
15-20 mo follow-up
to properties intrinsic to fetal skin cells (23,24). The exact mechanisms involved in this highly efficient repair have not yet been fully elucidated
8-9 yr follow-up
(25). Understanding the differences between fetal and adult wound healing properties is of particular
These biological dressings are not
today, they still require accredited
interest for the scientific community
tissue grafts, as the progenitor cells
infrastructures for cell storage and
as it could open strategies for the
cannot be found in patient tissue
cell manipulation. As live progenitor
development of new therapeutic
after healing. However, surgeons
cells are used, the biological dressing
products for the treatment of acute
observe an improvement in the
shelf life is short.
and chronic wounds.
healing process due to a reduction of pain, a reduced need for skin grafts,
In
The Burn Unit at the CHUV developed
and an improved scar quality. A
by Lapp et al. (2013), a further
custom made biological bandages
10-year follow-up study of the first
biopharmaceutical formulation was
using fetal progenitor cells for the
pediatric
developed by integrating ovine fetal
treatment of second degree burns.
progenitor cells demonstrated the
progenitor cell extracts(28).
These are currently used under a
safety of the treatment as well as the
The progenitor cellular extract was
compassionate use exemption (26).
significantly improved viscoelastic
shown to induce dermal fibroblast
The dressings consist of fetal skin
properties of the skin( ).
proliferation in vitro demonstrating
patients
treated
with
27
addition,
as
documented
that the extract is biologically active.
progenitor cells stored in liquid production
The extract was incorporated in
seeded in a collagen matrix, and
is routinely used in the CHUV for
an oil-in-water cream and used
delivered to the patient within 24-48
severe burn patients. They require
topically on acute wounds (incision
hours. The dressings are changed
cGMP facilities and cannot be stored
or burns). Upon topical application,
every three days (with 3 to 6
once produced which highly restricts
rapid
applications depending on extent
the development potential of such
inflammation was observed.
and severity of the burn injury).
products. In the form they are used
nitrogen
which
are
revitalized,
Biological
bandage
wound
closure
with
low
6.
Elanix Progenitor Cells
BRINGING PROGENITOR CELL BASED SOLUTIONS TO THE WORLD
Elanix Biotechnologies is built on the
development for the wound care
soothe intimate discomfort, twinges,
conviction that progenitor cells have
management market. Under the
and feelings of dryness. SKINrepair® is
an important role to play in the future
project name FirstCover, Elanix is
formulated for application on the skin
of regenerative medicine. This paper
developing medical devices from
to soothe lesions, help regenerate
has set out to clarify somewhat the
fetal progenitor cell technology to
the epidermis, and accompany the
nature of progenitor cells and their
assist and accelerate the wound
process of scar management.
natural role in homeostasis and tissue
healing process in patients suffering
repair, and to provide some evidence
not only from severe burns, but also
to support the adoption of progenitor
from diabetic foot, pressure ulcers,
cells for the development of tissue
and venous leg ulcers, all of which are
regeneration products.
currently underserved conditions.
The progenitor cell technology at the heart of Elanix Biotechnologies has
Elanix
aims
to
transform
the
The company’s current portfolio consists
been systematically proven to be safe,
experience gained in the use of
of Advanced Skin Care products
without known side-effects or adverse
biological wound dressings, a tech-
GYNrepair
reactions,
nology for highly controlled clinical
contain the CFPC®, a cell free protein
positive results towards its intended
environments, into products that
extract from animal progenitor cells.
goal: the acceleration of natural
can be distributed widely, easily
These products are directly derived
tissue regeneration. Elanix’ mission is
and durably stocked with no loss of
from Professor Applegate’s research
to replicate these successful results
efficacy, and applied successfully with
(28, 29) and are shown to relieve patients’
in the products which it brings to
relative ease. This industrialization
symptoms and promote healing.
market. These technologies have the
process is what Elanix is tackling
GYNrepair® is formulated for the
potential to bring significant benefit
in its current phase of product
external genital mucosa and used to
to patients worldwide.
®
and SKINrepair , which ®
and
has
yielded
very
7.
Elanix Progenitor Cells
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