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Current Stem Cell Research & Therapy
ISSN: 1574-888X
Current Stem
Cell Research & Therapy
Volume 3, Number 1, January 2008
Contents
Stem Cell Fate Decisions: The Role of Heparan Sulfate in the
Control of Autocrine and Paracrine Signals Pp.
1-8
Martin Grünert, Victor Nurcombe and Simon M. Cool
[Abstract]
Self-Renewal Versus Differentiation in Hematopoietic
Stem and Progenitor Cells: A Focus on Asymmetric Cell Divisions
Pp. 9-16
Bernd Giebel and Ingmar Bruns
[Abstract]
Cancer Stem Cell Model in Oral Squamous Cell Carcinoma
Pp. 17-20
Zeng-Tong Zhou and Wei-Wen Jiang
[Abstract]
Advances in Tissue and Organ Replacement
Pp. 21-31
Anthony Atala
[Abstract]
Mesenchymal Stem Cells: An Emerging Tool for Cancer Targeting
and Therapy Pp. 32-42
Vanessa Fritz and Christian Jorgensen
[Abstract]
Mesenchymal Stem Cells as Mediators of Neural Differentiation
Pp. 43-52
Steven A. Hardy, Daniel J. Maltman and Stefan A. Przyborski
[Abstract]
Stem Cells and βλαστημa
Cells Pp. 53-54
Panagiotis A. Tsonis
[Abstract]
Breast Cancer, a Stem Cell Disease Pp. 55-65
Rogelio González-Sarmiento and Jesús Pérez-Losada
[Abstract]
Current Concepts in Reprogramming Somatic Cells to
Pluripotent State Pp. 66-74
Jin Han and Kuldip S. Sidhu
[Abstract]
Abstracts
[Back to top]
Stem Cell Fate Decisions: The Role of Heparan Sulfate in the
Control of Autocrine and Paracrine Signals
Martin Grünert, Victor Nurcombe and Simon M. Cool
The aim of this review is to explore the idea that the
glycosaminoglycan sugar heparan sulfate (HS), richly concentrated
on the plasma membrane of all animal cells studied so far
and a major component of extracellular matrices, is by virtue
of its ability to modulate protein gradients and signal transduction,
the master regulator of stem cell fate (and thus wound healing).
Moreover, the interaction between HS and members of the TGF-β
superfamily is emerging as a central tenet for stem cells.
The potential significance of this interaction is best understood
by examining both how HS modulates ligand interactions and
stability, and how it maintains protein gradients with varying
degrees of specificity. Importantly, HS also regulates the
activity of numerous antagonists, thus underscoring its importance
as a primary regulator of stem cell fate decisions.
[Back to top]
Self-Renewal Versus Differentiation in Hematopoietic
Stem and Progenitor Cells: A Focus on Asymmetric Cell Divisions
Bernd Giebel and Ingmar Bruns
Like other somatic stem cells, hematopoietic stem cells
(HSC) have the ability to either self-renew or to differentiate.
They are essentially required for the hematopoietic homeostasis.
In this context HSC do not only need to replenish peripheral
blood cells of all lineages, but also have to keep their pool
relatively constant. Since disruption of the underlying control
mechanisms can lead to degeneration or expansion of the HSC-pool
as it occurs after irradiation or in leukemia, it is an important
concern to unveil mechanisms that govern the decision of self-renewal
versus differentiation in HSC-biology. There is good
evidence that certain extrinsic cues provided in a special
environment, the HSC-niches, essentially take part in regulating
the HSC-pool in vivo and might also be involved in
leukemogenesis. Apart from that, asymmetric cell divisions
seem to be another control instance in hematopoietic homeostasis.
It has been shown that siblings of primitive hematopoietic
cells often adopt different cell fates, and very recently
we identified four proteins that segregate asymmetrically
in a proportion of dividing primitive hematopoietic cells.
Whether asymmetric cell division participates in leukemogenesis,
remains to be investigated. However, on the example of neural
stem cells of the Drosophila larvae, the neuroblasts,
asymmetrically segregating molecules have been identified,
i.e. the tumor suppressor protein Brat and the transcription
factor Prospero, that are required to suppress self-renewal
in one of the arising daughter cells and whose loss of
function results in tumor formation. These findings provide
an attractive model of how defects in the process of asymmetric
cell divisions might transform normal HSC/HPC into leukemic
cells.
[Back to top]
Cancer Stem Cell Model in Oral Squamous Cell Carcinoma
Zeng-Tong Zhou and Wei-Wen Jiang
The concept of “field cancerization” describes
the presence of histological abnormal tissue surrounding oral
squamous cell carcinoma (OSCC). Molecular model of multistep
carcinogenesis indicates that an accumulation of genetic alterations
forms the basis for the OSCC progression with genetic heterogeneity.
Furthermore, we reviewed cancer stem cell (CSC) model, which
suggests functional heterogeneity in the tumor mass and current
supporting evidence in OSCC. According to CSC model, prevention
from carcinogen exposure and eliminating the particular CSCs
instead of targeting tumor mass could help obtain a more long-lasting
therapeutic effect.
[Back to top]
Advances in Tissue and Organ Replacement
Anthony Atala
Applications of regenerative medicine technology may
offer new therapies for patients with injuries, end-stage
organ failure, or other clinical problems. Currently, patients
suffering from diseased and injured organs can be treated
with transplanted organs. However, there is a shortage of
donor organs that is worsening yearly as the population ages
and new cases of organ failure increase. Scientists in the
field of regenerative medicine and tissue engineering are
now applying the principles of cell transplantation, material
science, and bioengineering to construct biological substitutes
that will restore and maintain normal function in diseased
and injured tissues. The stem cell field is a rapidly advancing
aspect of regenerative medicine as well, and new discoveries
here create new options for this type of therapy. For example,
therapeutic cloning, in which the nucleus from a donor cell
is transferred into an enucleated oocyte in order to extract
pluripotent embryonic stem cells from the resultant embryo,
provides another source of cells for cell-based tissue engineering
applications. While stem cells are still in the research phase,
some therapies arising from tissue engineering endeavors have
already entered the clinical setting, indicating that regenerative
medicine holds promise for the future.
[Back to top]
Mesenchymal Stem Cells: An Emerging Tool for Cancer Targeting
and Therapy
Vanessa Fritz and Christian Jorgensen
Mesenchymal stem cells (MSCs) from post-natal bone marrow
possess tremendous potential for cell-mediated gene therapy
in several disease processes, and recent reports have broadened
the spectrum for therapeutic applications to cancer therapy.
The evidence that sites of active tumorigenesis favor the
homing of exogenous MSCs have support the rationale for developing
engineered MSCs as a tool to track malignant tissues and deliver
anticancer agents within the tumor microenvironment. Several
reports have proven the efficiency of MSCs as cell carrier
for in vivo delivery of various clini-cally relevant
anticancer factors, including cytokines, interferon, pro-drugs
or replicative adenovirus, and tumor growth inhibition following
engraftment within or in the vicinity of tumor. The enthusiasm
for MSCs is further reinforced by the striking observation
that unmodified MSCs can exert antitumorigenic activity, and
preliminary reports in immunocompetent animals have provided
encouraging results for the use of MSCs in cancer immunotherapy.
This review highlights recent works and potential clinical
applications of MSCs in this field.
[Back to top]
Mesenchymal Stem Cells as Mediators of Neural Differentiation
Steven A. Hardy, Daniel J. Maltman and Stefan A. Przyborski
Mesenchymal stem cells (MSCs) represent a promising source
of material for autologous cell transplantation therapies,
in particular, their potential use for the treatment of damaged
nervous tissue. Much of the work in this area has focused
on the transplantation of MSCs into animal models of neurological
disorders, including stroke and spinal cord injury. Although
numerous studies have reported significant functional improvements
in these systems, the exact mechanism(s) by which MSCs elicit
recovery remains largely undefined. While it has been proposed
that ‘trans’-differentiation and/or cell fusion
events underly MSC-mediated neural repair, there is considerable
doubt that the low frequency of these phenomena is sufficient
to account for the observed levels of recovery. Furthermore,
in vitro studies call into question the ability of
MSCs to produce authentic neural derivatives. In this review
we focus on recent evidence indicating that transplanted MSCs
promote endogenous repair of neurologically damaged areas
via the release of soluble trophic factors and cytokines.
Through the modern analysis of MSC-conditioned media it is
becoming possible to gain new insight into the release and
interplay of these soluble factors and their neurogenic effects.
Ultimately this understanding may lead to the rational design
of new therapies for the treatment of neurological and neurodegenerative
disorders.
[Back to top]
Stem Cells and βλαστημa
Cells
Panagiotis A. Tsonis
Recently much effort has resulted in papers on how stem
cells can be generated from adult tissues in mice, but the
salamanders do this routinely. Salamanders can regenerate
most of their body parts, such as limbs, eyes, jaw, brain
(and spinal cord), heart, etc. Regeneration in salamanders
starts by dedifferentiation of the terminally differentiated
tissues at the site of injury. The dedifferentiated cells
can then differentiate to reconstitute the lost tissues. This
transdifferentiation in an adult animal is unprecedented among
vertebrates and does not involve recruitment of stem cells.
One of the ideas is that such reprogramming of terminally
differentiated cells might involve mechanisms that are similar
to the maintenance of embryonic stem cells. In the stem cell
field much emphasis has been recently given to the reprogramming
of adult cells (such as skin fibroblasts) to revert to ES
or pluripotent stem cells. It is our conviction that generation
of dedifferentiated cells in salamanders and stem cells, such
as the ones seen in repair in mammals share molecular signatures.
This mini review will discuss these issues and ideas that
could unite the stem cell biology with the classical regeneration
models.
[Back to top]
Breast Cancer, a Stem Cell Disease
Rogelio González-Sarmiento and Jesús Pérez-Losada
Breast cancer is a first magnitude problem of public
health worldwide. There is increasing evidence that this cancer
is originated in and maintained by a small population of undifferentiated
cells with self-renewal properties. This small population
generates a more differentiated pool of cells which represents
the main mass of the tumor, resembling the hierarchical tissue
organization of the normal breast. These cancer stem cells
seem to share a similar phenotype with their normal counterparts
but they display dysfunctional patterns of proliferation and
differentiation, and they no longer respond to normal physiological
controls that ensure a balanced cellular turnover. The origin
of these cancer stem cells is controversial; it is not well
known if they are originated from normal stem cells or from
more differentiated progenitors where a de novo stem
cell program is activated by the oncogenic insult. Here we
review the origin of breast cancer stem cells and their role
in the pathogenesis of cancer development, together with their
implications in breast cancer progression, treatment and prognosis.
[Back to top]
Current Concepts in Reprogramming Somatic Cells to
Pluripotent State
Jin Han and Kuldip S. Sidhu
Recently considerable interests have been roused in nuclear
reprogramming by somatic cell nuclear transfer using an egg
cytoplasm and/or by other means, such as fusion, cell extracts
treatment and genes transfections. However, the very mechanism
of reprogramming still remains elusive. Epigenetic modifications,
which play a significant role in normal mammalian development
in vivo is also involved in the process of reprogramming
in vitro. The latter shares some of the other features
observed in nuclear reprogramming in vivo. In this
review, we discuss the main epigenetic changes involved in
nuclear reprogramming and currently available approaches to
achieve nuclear reprogramming in vitro and its future
prospects.
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