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Paralysed rats have been enabled to walk again,
by transplanting nerve cells derived from human embryonic stem cells
into the animals. The findings add to a growing number of studies
that suggest that embryonic stem cells could have a valuable role
to play in treating spinal injuries. The researchers say trials
on people using this technique could start in about two years time.
Researchers are exploring a number of approaches to enable recovery
from spinal-cord injury, including drugs that overcome spinal cells'
reluctance to re-grow, ways of bridging the gap between severed
nerves, and transplants of various tissues, including adult stem-cells
derived from bone marrow, and nerve cells from the nose. Human trials
of some treatments, such as that using nose cells, have already
begun. But the first stem-call trials will be on patients
with recent spinal cord injuries and localised damage; treating
people who have been paralysed for years, or who suffer from degenerative
nerve diseases, is more difficult.
Ways will also have to be found to prevent people rejecting the
stem cells. One possible alternative to immunosuppressant drugs
would be to first give the patient bone-marrow stem cells from the
same source as the nerve cells. This might trick the patient’s
immune system into developing tolerance.
But adult cells have serious limitations as a
mass-market treatment, because not many cells can be grown from
a single source. That is not a problem with embryonic stem cells
(ESCs). "One cell bank derived from a single embryo produces
enough neurons to treat 10 million Parkinson's disease patients",
says Thomas Okarma of the Geron company in California. What is more,
adult stem cells may not be as versatile. "At this moment,
there is very little hard evidence that a bone marrow stem cell
can turn into anything but blood, or that a skin stem cell can become
anything but skin", he says. ESCs, on the other hand, have
the potential to develop into practically any type of tissue.But
there is nevertheless a serious problem with ESCs. "Undifferentiated
human embryonic stem cells have a very high probability of forming
tumours," says Hans Keirstead at the University of California,
Irvine, whose team has performed the latest research. To prevent
this, his team turned ESCs into specialised cells before transplanting
them. They transformed the ESCs into oligodendrocytes, the cells
that form the insulating layer of myelin that is vital for conducting
nerve impulses. Keirstead's team transplanted the oligodendrocytes
into rats with "bruised" spines. After nine weeks, the
rats fully regained the ability to walk, he says, whereas rats given
no therapy remained paralysed. The team repeated the experiment
on three separate occasions, with the same results. Analysis of
the rats' spinal cords revealed that the transplanted oligodendrocytes
had wrapped themselves around neurons and formed new myelin sheaths.
The transplanted cells also secreted growth factors that appear
to have stimulated the formation of new neurons.While many promising
spinal repair experiments have proved hard to reproduce, researchers
at Johns Hopkins University in Baltimore, Maryland, also announced
similar results last week. The team injected undifferentiated human
ESCs into rats with injured spinal cords. After 24 weeks, the treated
rats could support their own weight. Team leader Douglas Kerr thinks
the animals' recovery was not due to the growth of new cells, but
to the secretion of two growth factors (TGF-alpha and BDNF), which
protected damaged neurons and helped them to re-establish connections
with other neurons. "The stem cells' magic was really their
ability to get into the area of injury and snuggle up to those neurons
teetering on the brink of death," says Kerr, whose results
will appear in the Journal of Neuroscience.
" Umbilical cord blood stem cells are used as a part of the
therapy regimen for nearly 50 diseases today. One of the challenges
in developing additional cellular therapies is the need to multiply
and preserve large quantities of these powerful umbilical cord blood
stem cells for use in treating an even broader range of diseases.
These important studies indicate that we can substantially increase
the number of these valuable cells and freeze them for later use",
says Jan Visser of ViaCell.
Okarma hopes the results will help persuade policy
makers in Washington not to ban therapeutic cloning, which is one
way of obtaining human ESCs, and increase funding for ESC research.
"The promise of this technology is beginning to be realised",
he says. "That's why we think this battle is worth fighting."
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Centre for Neuroscience, The University
of Melbourne, Melbourne, VIC 3010, Australia.
One of the most exciting possibilities
in human therapeutics is that stem cells (embryonic or adult)
may compensate for cell loss in disease, with functional recovery.
This has received considerable publicity in the lay press.
Much work remains to be done to turn stem cell therapy into
a practical reality for major degenerative diseases, especially
those affecting the nervous system. Medical scientists and
journalists should work together in ensuring that the general
public has a realistic understanding of the likely time frame
in which benefits from stem cell therapies will be realised.
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Department of Vascular Medicine, University
Medical Center, Utrecht, The Netherlands.
Glomerular endothelial injury plays
an important role in the pathogenesis of renal diseases
and is centrally involved in renal disease progression.
Glomerular endothelial repair may help maintain renal function.
We examined whether bone-marrow (BM)-derived cells contribute
to glomerular repair. A rat allogenic BM transplant model
was used to allow tracing of BM-derived cells using a donor
major histocompatibility complex class-I specific mAb. In
glomeruli of chimeric rats we identified a small number
of donor-BM-derived endothelial and mesangial cells, which
increased in a time-dependent manner. Induction of anti-Thy-1.1-glomerulonephritis
(transient mesangial and secondary glomerular endothelial
injury) caused a significant, more than fourfold increase
in the number of BM-derived glomerular endothelial cells
at day 7 after anti-Thy-1.1 injection compared to chimeric
rats without glomerular injury. The level of BM-derived
endothelial cells remained high at day 28. We also observed
a more than sevenfold increase in the number of BM-derived
mesangial cells at day 28. BM-derived endothelial and mesangial
cells were fully integrated in the glomerular structure.
Our data show that BM-derived cells participate in glomerular
endothelial and mesangial cell turnover and contribute to
microvascular repair. These findings provide novel insights
into the pathogenesis of renal disease and suggest a potential
role for stem cell therapy.
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Departement d'Hematologie and Institut
de Recherche en Hematologie et Transfusion, Hopitaux de
Mulhouse, 87 Avenue d'Altkirch, Mulhouse, France.
Over the past few years, research
on animal and human stem cells has experienced tremendous
advances which are almost daily loudly revealed to the public
on the front-page of newspapers. The reason for such an
enthusiasm over stem cells is that they could be used to
cure patients suffering from spontaneous or injuries-related
diseases that are due to particular types of cells functioning
incorrectly, such as cardiomyopathy, diabetes mellitus,
osteoporosis, cancers, Parkinson's disease, spinal cord
injuries or genetic abnormalities. Currently, these diseases
have slightly or non-efficient treatment options, and millions
of people around the world are desperately waiting to be
cured. Even if not any person with one of these diseases
could potentially benefit from stem cell therapy, the new
concept of "regenerative medicine" is unprecedented
since it involves the regeneration of normal cells, tissues
and organs which could allow to treat a patient whereby
both, the immediate problem would be corrected and the normal
physiological processes restored, without any need for subsequent
drugs. However, conflicting ethical controversies surround
this new medicine approach, inside and outside the medical
community, especially when human embryonic stem cells (h-ESCs)
are concerned. This ethical debate on clinical use of h-ESCs
has recently encouraged.
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Several recent discoveries have shifted
the paradigm that there is no potential for myocardial regeneration
and have fueled enthusiasm for a new frontier in the treatment
of cardiovascular disease-stem cells. Fundamental to this
emerging field is the cumulative evidence that adult bone
marrow stem cells can differentiate into a wide variety
of cell types, including cardiac myocytes and endothelial
cells. This phenomenon has been termed stem cell plasticity
and is the basis for the explosive recent interest in stem
cell-based therapies. Directed to cardiovascular disease,
stem cell therapy holds the promise of replacing lost heart
muscle and enhancing cardiovascular revascularization. Early
evidence of the feasibility of stem cell therapy for cardiovascular
disease came from a series of animal experiments demonstrating
that adult stem cells could become cardiac muscle cells
(myogenesis) and participate in the formation of new blood
vessels (angiogenesis and vasculogenesis) in the heart after
myocardial infarction. These findings have been rapidly
translated to ongoing human trials, but many questions remain.
This review focuses on the use of adult bone marrow-derived
stem cells for the treatment of ischemic cardiovascular
disease and will contrast how far we have come in a short
time with how far we still need to go before stem cell therapy
becomes routine in cardiovascular medicine.
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Due to autoimmune destruction of
insulin-producing pancreatic b-cells, type 1 diabetic patients,
and also patients with type 2 diabetes suffering from defective
insulin secretion rely on lifelong substitution with insulin.
A clinically established alternative therapy for diabetics
with exogenous insulin substitution, the transplantation
of human islets of Langerhans, is limited by the lack of
donor organs. The intensive search for new sources of pancreatic
b-cells now focuses on human stem cells. Insulin-producing
cells for transplantation can be generated from both embryonic
and adult pancreatic stem cells. Both types of stem cells,
however, differ with respect to availability, in vitro expansion,
potential for differentiation, and tumorigenicity, which
is elucidated by the authors. Before stem cell therapeutic
strategies for diabetes mellitus can be transferred to clinical
application in humans, aspects of functional effectivity,
safety, and cost-effectiveness have to be solved. Considering
these prerequisites in the Diskuslight of currently available
therapeutic options, however, it can be estimated, that
stem cell therapy for diabetes mellitus may be cost-effectively
introduced into clinical routine in the future.
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