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The Many Mysteries of Stem Cells

Emerging field befuddled by questions of science, ethics

FRIDAY, April 29, 2005 (HealthDay News) -- At its most basic, the hope of stem cell research is to make human beings more like salamanders.

When chopped into bits, salamanders regenerate.

Humans don't.

By exploiting an elegant natural process -- the body's ability to heal itself with stem cells -- scientists are hoping to find therapies or cures for a long list of conditions including spinal cord paralysis, heart failure and Alzheimer's.

"Humans have a mechanism that sort of dampens down that ability. Infusions of stem cells are basically overcoming the damping-down mechanism," said Dr. Brian Butcher, associate director of the Tulane Center for Gene Therapy in New Orleans.

The center is the only National Institutes of Health-sponsored organization to distribute adult stem cells to other academic researchers around the world.

"Stem cells have the potential to completely change medicine and public health," added Dr. Paul Whelton, senior vice president for health sciences at Tulane University.

And that has already begun, even though most of the "breakthroughs" in stem cell research thus far have occurred in the laboratory. These include tantalizing possibilities that stem cells can reverse damage from heart attacks or spur the growth of new brain cells. One landmark study in the 1990s used stem cells from siblings' bone marrow to help children with brittle bone condition.

But even as the science progresses, albeit haltingly, attempts to regulate and codify this new field have been less than elegant.

Earlier this week, in what some saw as an attempt to fill a vacuum left by the federal government, the National Academy of Sciences issued a proposal for guidelines to govern research with human embryonic stem cells, the most controversial type of stem cell.

Among other things, the guidelines called for establishing Embryonic Stem Cell Research Oversight (ESCRO) committees, to review research; requiring the consent of anonymous sperm donors when embryos from IVF clinics are used; restricting the creation of chimeras, which result when human cells are mixed with animal cells; prohibiting the breeding of any animals that contain human embryonic stem cells, and restricting any payments to donors beyond reimbursement of direct expenses.

"Our hope is that this will provide an ethical foundation in which stem cell research can continue," said Dr. Bruce Albert, president of the National Academy of Sciences.

"There are no federal regulations governing stem cell research and no system for oversight," said Richard O. Hynes, co-chairman of the committee that prepared the guidelines. "This has led to a great deal of uncertainty in the public . . . and concern on the part of scientists who would like to do research appropriately. These guidelines aim to encourage responsible practices in embryonic stem cell research, regardless of the source of funding, the derivation or the use."

But while many uncertainties are of an ethical nature, at least as many are of a scientific nature. Just ask Tulane University researchers.

Tulane has circumvented many of the ethical issues by dealing only in adult stem cells and, when dealing with actual patients, only in autologous infusions. That means the stem cells come from one patient and go back to the same patient, reducing the likelihood of rejection.

But that still leaves a vast domain of unanswered questions.

For research, the center relies on donations of bone marrow: A person can donate once every two months and be compensated $220 for giving marrow from both hips, a procedure that takes about 15 minutes.

A teaspoon of bone marrow, cultured delicately, can yield about 300 million stem cells in two weeks.

But there's debate about how best to grow these stem cells.

At Tulane, experts say they get the best results by not crowding the cells, hence they have 50 cells per centimeter squared versus 5,000 at many other facilities. "We need to pamper cells," said Radhika Pochampally, research instructor at the Tulane Center for Gene Therapy. "They don't like crowds. They need a lot of nutrients. We have to change the culture conditions according to the donor."

Tulane's Gene Therapy Center is betting on adult stem cells from bone marrow for a clinical trial on spinal cord paralysis they plan to begin within the next year.

In the next building on Tulane Avenue, other scientists are betting on the future of adult stem cells drawn from fat.

The most potent stem cells are not likely to be from bone marrow, said Dr. Eckhard Alt, a professor of medicine at Tulane School of Medicine. "The renewal force is local and associated with vessels," he explained.

In other words, when the body needs to renew itself, it is unlikely to go to the remote regions of bone marrow. It is more likely to get stem cells from somewhere close and accessible, Alt said.

Alt and his colleagues are hoping their research will one day lead to a trials using fat stem cells to combat heart failure.

The different Tulane "factions," at least, seem to agree that adult stem cells are superior to embryonic stem cells because they don't increase the risk of cancer later in a person's life. (There has been one report of adult stem cells increasing the risk of cancer, but it was only one and happened in a Petri dish, not a person.) And adult stem cells grow quickly without needing feeder cells.

But then there's the widely acknowledged point that embryonic stem cells have a greater capacity to differentiate into more tissue than adult stem cells.

There's also the issue of placental or cord blood stem cells, as well as the issue of which stem cells might be best for lung repair or for heart repair.

"There's not one snake oil for all," said Dr. Darwin Prockop, director of the Tulane Center for Gene Therapy.

There are also questions about whether all bone marrow stem cells are created equal. In fact, there may be as many as 10 different types of stem cells in the bone marrow, Prockop pointed out. "We may be using different cells without knowing it," he noted.

There are questions about how stem cells, when left to their own devices, manage to find tissues that are damaged. And questions about when a stem cell is an embryonic stem cell and when it is an adult stem cell.

For all the pages of guidelines developed by the National Academy of Sciences, or the billions of dollars being devoted by states to cultivate stem cell research, the most basic processes of the human body remain a mystery to even the most trained and enlightened.

"This research is still somewhere between science and art," Prockop said.

More information

The National Institutes of Health has more on stem cells.

SOURCES: Brian Butcher, M.D., associate director, Tulane Center for Gene Therapy, New Orleans; Paul Whelton, M.D., senior vice president, health sciences, Tulane University, New Orleans; Radhika Pochampally, Ph.D., research instructor, Tulane Center for Gene Therapy, New Orleans; Darwin Prockop, M.D., Ph.D., director, Tulane Center for Gene Therapy, New Orleans; Eckhard Alt, M.D., professor, medicine, Tulane University School of Medicine, New Orleans; April 26, 2005, news conference with Richard O. Hynes, Ph.D., investigator, Howard Hughes Medical Institute; Daniel K. Ludwig, Professor of Cancer Research, Center for Cancer Research and Department of Biology, Massachusetts Institute of Technology, Cambridge; Bruce Albert, M.D., president, National Academy of Sciences; New York Times
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