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Current
Stem Cell Research & Therapy
ISSN: 1574-888X
Current Stem
Cell Research & Therapy
Volume 2, Number 4, December 2007
Contents
Small RNAs, Big Potential: The Role of MicroRNAs in Stem Cell
Function Pp. 264-271
Kara M. Foshay and G. Ian Gallicano
[Abstract]
Participation of Adult Bone Marrow-Derived Stem
Cells in Pancreatic Regeneration: Neogenesis Versus Endogenesis
Pp. 272-279
Svetlana Iskovich, Ayelet Kaminitz, Michal Pearl Yafe,
Keren Mizrahi, Jerry Stein, Isaac Yaniv and Nadir Askenasy
[Abstract]
Stem Cells as In Vitro Models of Disease
Pp. 280-292
Pilar Ruiz-Lozano and Prithi Rajan
[Abstract]
Therapeutic Potential of Stem/Progenitor Cells
in Human Skeletal Muscle for Cardiovascular Regeneration
Pp. 293-300
Tetsuya Nomura, Eishi Ashihara, Kento Tateishi, Tomomi
Ueyama, Tomosaburo Takahas-hi, Masaaki Yamagishi, Toshikazu
Kubo, Hitoshi Yaku, Hiroaki Matsubara and Hidemasa Oh
[Abstract]
Umbilical Cord Blood: A Unique Source
of Pluripotent Stem Cells for Regenerative Medicine
Pp. 301-309
David T. Harris and Ian Rogers
[Abstract]
Mesenchymal Stromal Cells from Umbilical Cord Blood
Pp. 310-323
Karen Bieback and Harald Klüter
[Abstract]
Expansion of Umbilical Cord Blood for Clinical
Transplantation Pp. 324-335
David N. Haylock and Susan K. Nilsson
[Abstract]
Abstracts
[Back to top]
Small RNAs, Big Potential: The Role of MicroRNAs in Stem
Cell Function
Kara M. Foshay and G. Ian Gallicano
MicroRNAs (miRNAs) are a newly discovered, yet powerful
mechanism for regulating protein expression via mRNA
translational inhibition. Loss of all miRNA function within
mice leads to embryonic lethality with a loss of the stem
cell population in the epiblast and failure to form a primitive
streak. These data suggest that miRNAs play a major role in
embryonic development. As critical regulation of protein expression
is also important for controlling the balance between self-renewal
and differentiation in stem cells, the study of miRNAs within
this model system is rapidly expanding. New data suggest that
stem cells have discrete miRNA expression profiles, which
may account for, or contribute to, the intrinsic stem cell
properties of self-renewal and pluripotency. Specifically,
miRNAs have been implicated in downregulation of cell cycle
checkpoint proteins during germ stem cell division. Other
data demonstrate that changes in miRNA expression can promote
or inhibit stem or progenitor cell differentiation within
different cell lineages, including hematopoietic cells, cardiomyocytes,
myoblasts, and neural cells. In this review we detail the
established functional roles of miRNAs in the embryonic and
adult stem cell model systems. Finally, we explore new techniques
that exploit endogenous miRNA processing and function for
applications in basic and clinical research
[Back to top]
Participation of Adult Bone Marrow-Derived Stem Cells in Pancreatic
Regeneration: Neogenesis Versus Endogenesis
Svetlana Iskovich, Ayelet Kaminitz, Michal Pearl Yafe,
Keren Mizrahi, Jerry Stein, Isaac Yaniv and Nadir Askenasy
Regenerative medicine opens new avenues and promises
towards more effective therapies for autoimmune disorders.
Current therapeutic strategies for type I diabetes focus on
three major directions, with distinct advantages and disadvantages:
arrest of autoimmunity, islet transplantation and generation
of neoislets. There is mounting evidence that candidate stem
cells residing in the hematopoietic compartments participate
in regeneration of pancreatic islets following chemical and
autoimmune injury in vivo. The apparent major mechanisms
include immunomodulation, revascularization, support of endogenous
β-cell
regeneration and differentiation into insulin-producing cells.
Review of the current evidence suggests that some divergent
observations depend primarily on the experimental design,
which both limits and accentuates developmental events. The
flood of publications reporting negative results appears to
reflect primarily suboptimal experimental conditions for differentiation
of putative stem cells, rather than limited developmental
plasticity. Stem cells modulate the course of autoimmune diabetes
through multiple mechanisms, including de novo generation
of units capable to sense, produce and secrete insulin. Therefore,
the charged debate over controversies surrounding developmental
plasticity should not impede attempts to design curative therapies
for this disease.
[Back to top]
Stem Cells as In Vitro Models of Disease
Pilar Ruiz-Lozano and Prithi Rajan
Although the use of stem cells in cell-replacement therapies
by transplantation is obvious, another equally important and
interesting application of stem cells is to use them in disease
modeling. Disease models serve as a platform to dissect the
biochemical mechanisms of normal phenotypes and the processes
which go awry during disease conditions. Particularly in complex,
multigenic diseases, molecular studies lead to a greater understanding
of the disease, and perhaps more targeted approaches for therapies.
Stem cells provide an ideal in vitro system in which
to study events related to development at the molecular and
cellular level. Neural stem cells have been used as excellent
models to study the mechanisms of differentiation of cells
of the central nervous system. These studies may be particularly
relevant to diseases of complex etiology such as psychiatric
illnesses, neurodegenerative diseases and brain tumors. Stem
cell-derived systems are also being developed to create models
of cardiovascular disease. The application of stem cells to
the study of cardiovascular illnesses, and vertebrate heart
development, is discussed.
[Back to top]
Therapeutic Potential of Stem/Progenitor Cells in Human Skeletal
Muscle for Cardiovascular Regeneration
Tetsuya Nomura, Eishi Ashihara, Kento Tateishi, Tomomi
Ueyama, Tomosaburo Takahas-hi, Masaaki Yamagishi, Toshikazu
Kubo, Hitoshi Yaku, Hiroaki Matsubara and Hidemasa Oh
Although myoblast transplantation in patients with ischemic
heart failure results in a significant improvement of cardiac
function, subsequent studies have consistently shown the myotubes
formation in the absence of electromechanical coupling with
the neighboring host myocardium, accompanied with the short-term
release of paracrine effectors from implanted cells. One major
pitfall of using myoblasts is that transplanted cells do not
differentiate into cardiomyocytes, which may cause the inherent
proarrhythmogenic events. Therefore, whether a discrete subpopulation
in heterogeneous muscle-cell cultures is responsible for substantial
cardiovascular regeneration has yet to be investigated. We
describe here the isolation of progenitor cells from human
skeletal muscle. These cells proliferated as non-adherent
myospheres in suspension and displayed early embryonic factors
and mesenchymal cell-like characteristics. Flow cytometric
analyses demonstrated that CD56/N-CAM/Leu-19, a neural cell
adhesion molecule abundantly present in myoblasts, was absent
in myospheres but was expressed in an adherent cell population
containing myogenic precursors. Myosphere-derived progenitor
cells (MDPCs) differentiated in culture to produce cardiac,
smooth muscle, and endothelial cells. Transplantation of MDPCs
into ischemic hearts in NOD/scid mice promoted angiogenesis
with substantial cardiovascular regeneration. Our results
provide a foundation to further study the cell and biological
function of human MDPCs which may have potential therapeutic
implications.
[Back to top]
Umbilical Cord Blood: A Unique Source of Pluripotent Stem
Cells for Regenerative Medicine
David T. Harris and Ian Rogers
It is estimated that almost 1 in 3 individuals in the
United States might benefit from regenerative medicine therapy.
Unfortunately, embryonic stem (ES) cell therapies are currently
limited by ethical, political, biological and regulatory hurdles.
Thus, for the foreseeable future, the march of regenerative
medicine to the clinic will depend upon the development of
non-ES cell therapies. Current sources of non-ES cells easily
available in large numbers can be found in the bone marrow,
adipose tissue and umbilical cord blood. Each of these types
of stem cells has already begun to be utilized to treat a
variety of diseases. This review will show that cord blood
(CB) contains multiple populations of ES-like and other pluripotential
stem cells, capable of giving rise to hematopoietic, epithelial,
endothelial, and neural tissues both in vitro and
in vivo. Cumulatively, the identification and isolation
of these populations of pluripotent stem cells within cord
blood represents a scientific breakthrough that could potentially
impact every field of medicine, via their use in
regenerative medicine. Thus, CB stem cells are amenable to
treatment of a wide variety of diseases including cardiovascular,
hepatic, ophthalmic, orthopaedic, neurological and endocrine
diseases.
[Back to top]
Mesenchymal Stromal Cells from Umbilical Cord Blood
Karen Bieback and Harald Klüter
Mesenchymal Stromal Cells (MSC) are key candidates for
cellular therapies. Although most therapeutic applications
have focused on adult bone marrow derived MSC, increasing
evidence suggests that MSC are present within a wide range
of tissues. Umbilical cord blood (CB) has been proven to be
a valuable source of hematopoietic stem cells, but its therapeutic
potential extends beyond the hematopoietic component suggesting
regenerative potential in solid organs as well.
There is evidence that other stem or progenitor populations,
such as MSC, exist in CB which might be responsible for these
effects. Many different stem and progenitor cell populations
have been postulated with potential ranging from embryonic
like to lineage-committed progenitor cells. Based on the confusing
data, this review focuses on a human CB derived, plastic adherent
fibroblastoid population expressing similar characteristics
to bone marrow derived MSC. It concentrates especially on
concepts of isolation and expansion, comparing the phenotype
with bone marrow derived MSC, describing the differentiation
capacity and finally in the last the therapeutic potential
with regard to regenerative medicine, stromal support, immune
modulation and gene therapy.
[Back to top]
Expansion of Umbilical Cord Blood for Clinical Transplantation
David N. Haylock and Susan K. Nilsson
Since the first successful cord blood transplant was
performed in 1988 there has been a gradual increase in the
use of cord blood for hemopoietic stem cell transplantation.
Worldwide, over 8,000 unrelated cord blood transplants have
been performed with the majority being for children with hemopoietic
malignancies. Transplantation for adults has increased but
is limited by the low number of nucleated cells and CD34+
cells within a single cord blood collection. Cord blood hemopoietic
stem cells are more primitive than their adult counterparts
and have high proliferative potential. Cord blood ex vivo
expansion is designed to improve transplant outcomes by increasing
the number of hemopoietic stem cells with long term repopulating
potential and their differentiated progeny. However, despite
a large amount of research activity during the last decade,
this aim has not been realized. Herein we discuss the rationale
for this approach; culture methods for ex vivo expansion,
ways to assess the functional capacity of ex vivo
generated hemopoietic stem cells and clinical outcomes following
transplantation with ex vivo expanded cord blood.
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