Embryonic hope for damaged spines

July 02, 2003

NERVE cells derived from human embryonic stem cells and transplanted into paralysed rats have enabled the animals to walk again. The findings add to a growing number of studies that suggest embryonic stem cells could have a valuable role to play in treating spinal injuries.

The researchers, whose work was funded by stem cell giant Geron of Menlo Park, California, say trials on people could start in just two years. But the first trials are likely to involve patients with recent spinal cord injuries and localised damage. Treating people who have been paralysed for years or suffer from degenerative nerve diseases would be far more difficult.

Ways will also have to be found to prevent people rejecting the stem cells. One possible alternative to immunosuppressant drugs, Geron president Thomas Okarma told the meeting last week, would be to first give patients bone marrow stem cells from the same source as the nerve cells. This might trick the patients' immune system into developing tolerance.

Researchers are exploring a number of approaches to repairing damaged spines, including drugs that overcome spinal cells' reluctance to regrow, 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 using nose cells, have already begun.

But Okarma thinks 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 Okarma.

What's more, he claims, 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." ESCs, on the other hand, have the potential to develop into practically any type of tissue.

But there is also 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 did 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.

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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