November 2001

Adult Stem Cells

Continued from page 1

By Stephen S. Hall

Sprinkled in tissues throughout the body, from just below the surface of the skin to deep redoubts like the liver and bone marrow, adult stem cells are not, critics say, the answer to every ill. "For certain diseases, adult cells appear very promising, for hepatic and cardiac diseases in particular," says Ronald McKay, a researcher at the National Institutes of Health. "However, if you're asking for a solution to Parkinson's disease or diabetes, I would say the cells that offer the best way are fetal and embryonic." Still, in the unforgiving crucible of clinical studies, where medical potential meets the fickle realities of the human body, adult stem cells are already being tested, while the initial use of embryonic stem cells in humans is perhaps three to five years away.

While a number of biotech companies have adult stem cell research programs, Osiris has been especially aggressive about taking the cells into human trials. Since 1999, for example, doctors working with the company have been testing the ability of mesenchymal stem cells derived from bone marrow to help patients with cancer more quickly rebuild their blood and immune systems, which can be damaged by chemotherapy. In these studies, the mesenchymal stem cells were intended to enhance traditional bone marrow or umbilical-cord-blood transplants. "What we can say so far," says University of Minnesota professor of pediatrics John E. Wagner, who heads one of the studies, "is that we have seen no negative side effects, and we have the impression that it's faster."

Recent animal studies emerging from academic labs have underscored the major take-home lesson about adult stem cells in the past year or so: these cells are much more biologically versatile, and capable of adopting many more cellular fates, than anyone previously thought. Last May, pathologist Neil Theise of New York University and stem cell biologist Diane Krause of Yale University and their colleagues published a report in the journal Cell claiming that an adult stem cell from the bone marrow of mice had the capacity to form multiple tissues-blood, lung, liver, stomach, esophagus, intestines and skin. Theise believes these adult stem cells are as flexible as the embryonic kind, and he refers to them as the "ultimate adult stem cell." And a team led by Freda Miller of McGill University in Montral recently published work showing that adult stem cells plucked out of the skin, an easily accessible site for harvest, can develop into fat, muscle and neural cells.

Another similarly surprising wrinkle in the adult stem cell story has emerged in the last year in research at Stanford University and the National Institutes of Health. The lab of Eva Mezey at the National Institute of Neurological Disorders and Stroke, for example, has shown that, in mice, transplanted bone-marrow-derived stem cells can migrate to the brain and develop into cells with characteristics of neurons and other types of brain cells. It is part of a string of intriguing, but far from definitive, experiments suggesting that the fate of adult stem cells is determined to an enormous degree by the local environment in which they are placed.

Skeptics warn that stem cell experiments in mice don't automatically translate into human biology. Still, all these studies reinforce the notion that the adult body maintains a reserve of stem cells, certainly in the bone marrow and probably in many other tissues as well-although the supplies seem to dwindle with age. "They seem to be part of a natural repair system, so that when you damage a tissue, they come from the marrow in large numbers," says Darwin J. Prockop, director of Tulane University's Center for Gene Therapy in New Orleans, LA. In other words, adult stem cells appear to act as the body's on-call, 24-hour-a-day microscopic medical dispensary for wound repair.