Promising Way to Repair Brain 
Less controversial, more plentiful source of stem cells reported
Carl T. Hall / SF Chronicle 6nov00

Primitive brain cells taken from cadavers have the stunning ability to regenerate into healthy, living neurons, scientists reported yesterday.

The findings, reported at the annual meeting of the Society for Neuroscience, may point to a plentiful new source of neuronal stem cells, as the primitive cells are called, that avoids the ethical controversies and practical limits of using cells derived from fetal tissue.

Researchers also reported promising early results yesterday using stem cells to treat even some of the most difficult brain conditions, including head trauma, spinal cord injuries and stroke, which can often cause damage considered beyond the reach of modern medicine.

``One of the surprises has been the adaptability of stem cells taken from a multiplicity of sources,'' said Dr. Ira Black of the Robert Wood Johnson Medical School in New Jersey.

MANY UNANSWERED QUESTIONS

The seemingly limitless potential of stem cells was tempered, however, by new warnings about the many unknowns surrounding stem cells and their potential risks when used as therapy in humans, ranging from cancer to deadly inflammation of the spinal cord. Nor is it clear that improvements in brain function being observed so far, mainly in experiments with laboratory animals, can be duplicated in humans.

Clinical trials are under way involving stem cell transplants in people with Parkinson's, brought on by a loss of specialized neurons that produce the neurotransmitter dopamine. Although a definitive long-term benefit has yet to be shown, signs so far suggest that stem cells can replace these lost ``dopaminergic'' cells.

There is a risk that cells used for transplants might cause problems of their own, including immune disorders and malignancies. In the case of autopsy-derived cells, there are risks of prion diseases, forcing researchers to take extra precautions, even in handling the tissue samples.

So, for the next two years or so, human stem cell trials will be extremely limited, involving only a handful of patients and focused mainly on sorting out the basic biology and safety concerns, experts said.

Despite the caveats, there is a growing sense of excitement that stem cells might become the key tools in futuristic brain repair procedures.

About 28,000 people are attending the five-day neuroscience meeting here, by far the largest gathering of brain specialists in the world. And while the discussions run the gamut from basic research on the brain and emotion to clinical application of new drugs, findings of new sources and uses of stem cells quickly emerged as a major theme.

After a long build-up in basic research, ``We are entering the era of experimental therapeutics,'' said Dr. Donald Price of Johns Hopkins University School of Medicine.

Stem cells are an immature form of cell with a remarkable power to transform themselves into virtually any of the thousands of types of cells that make up human bodies. Stem cells from the nervous system can be turned into the building blocks of bone and muscle, and cells from the bone marrow can be made into neurons, or nerve cells.

COULD EASE MANY CONDITIONS

Now, scientists are finding this transformative power might be potent therapy in a wide assortment of conditions afflicting the nervous system. Stem cells were once thought to be a hallmark of early fetal development, disappearing in children and adults, which limited their use and made it difficult even to conduct experiments.

But it turns out that even older adults still have quiescent, but durable, stem cells capable of differentiating into specific types of neurons.

Nerve cells need copious amounts of oxygen to survive and so die quickly when the person dies. Not so with stem cells, reported Theo Palmer, a neuroscientist at Stanford University, and Fred Gage at the Salk Institute in San Diego.

They found that stem cells could be isolated from autopsy samples taken as long as 24 hours after death of the donor, and then coaxed into reproducing in a laboratory dish. The cells are far more abundant and more active in younger people, but a few hardy precursors of nerve cells were found in the case of one 72- year-old, Palmer said.

The question now being examined is what prompts the cells to become active and how they might be engineered into cells suitable for therapeutic transplant. One reason for optimism is that stem cells have a mysterious ability to migrate to an area of brain injury, detect which type of brain cell is missing, and then turn into the missing cell type.

PROMISING EXPERIMENTS

Tracy McIntosh at the University of Pennsylvania and Dr. Evan Snyder of Harvard Medical School reported for the first time that stem cells can be transplanted into adult mice with traumatic brain injury and restore function. Even cells placed on the side of the brain opposite the injury were shown to have moved into place.

During a 12-week study period, the animals were shown to have achieved ``dramatic improvement'' in motor functions completely absent before the transplant. Just what caused that improvement remains to be seen. It seems likely that the stem cells replaced the damaged nerve cells, but it's also possible that they brought along some helpful growth factors as they migrated, or even merely provided structural or chemical support for neurons that had somehow survived the injury.

LINGERING MYSTERIES

And how the stem cells, which have no obvious means of locomotion, manage to propel themselves, and what prompts them to move or guides them along, is equally a mystery. Researchers said it will be important to clear up some of those questions before human testing can expand to the stage of multicenter trials enrolling hundreds of patients.

Clearly, there's a desperate need for something to happen quickly, McIntosh noted, pointing out that the only existing treatment for head trauma consists of drilling holes into the skull in order to relieve pressure -- essentially the same strategy used by the ancient Incas and Mayans.

``We really haven't become any more sophisticated,'' he said.

Finding plentiful new supplies of stem cells might help by sidestepping the ethical battles over use of fetal sources, but those ethical issues do not appear likely to disappear altogether, at least not anytime soon. That's because the fetal cells are still considered the benchmark against which all the other cell types are measured.

It is also likely that fetal cells have characteristics that may not be found elsewhere, forcing researchers to rely on fetal sources until the factors that give rise to these special traits are better understood.