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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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