One of the hottest areas of stem cell research would seem to be beyond the reach of adult stem cells: the brain. The problem, as Harvard Medical School researcher Evan Snyder bluntly puts it, is, “If you’re talking about the brain, where would the adult stem cells come from?”Fred Gage, a neuroscientist at the Salk Institute for Biological Studies in La Jolla, CA, whose group was the first to find adult neural stem cells in the mammalian brain, has offered a potential rejoinder. Earlier this year, Gage’s team extracted what he calls adult neural progenitor cells from cadavers-leading to the possibility of harvesting the cells from fresh cadavers for medical use, much as hearts, livers and kidneys are harvested from accident victims for organ transplants.
In animal experiments, the researchers have shown that transplanted neural stem cells-much like the bone-marrow-derived stem cells in Mezey’s experiments at the National Institute of Neurological Disorders and Stroke-can migrate to the zone in the brain where new neurological cells are formed and to areas of injury. The cells typically take on the shape and function of other cells in those spots. “Not only are new cells born, but they undergo synaptogenesis,” or create the ability to connect with other nerve cells, Gage said at a meeting on stem cell biology at Cold Spring Harbor Laboratory last March.
One of the most surprising findings in the area, though-from Mezey’s experiments and from a recent rat study conducted by Helen Blau’s group at Stanford-is that it might not be necessary to start with stem cells taken from the brain, since stem cells from bone marrow may be able to repair neurological damage. “If we could learn what the signals are and learn how to make it more robust,” Blau said at the Cold Spring Harbor meeting, “if we could get function [in these cells], and see if the cells migrate to damage, it might have great utility in the treatment of Parkinson’s disease, stroke and trauma.”
All those ifs reflect that scientists are in the early stages of research in a field rife with uncertainty-and peril. The research community received a sobering reality check last March when neuroscientist Curt Freed and colleagues at the University of Colorado reported in the New England Journal of Medicine mixed results in a clinical trial in which embryonic neural cells (but not specifically stem cells) were implanted in the brains of patients with Parkinson’s disease. Some of the patients experienced a small degree of improvement, but others developed severe and disabling side effects-constant, jerky motions-that were described as worse than the original symptoms of the disease. While the experiments did not specifically involve stem cells, the results served as a reminder that any cells, once implanted, can have not only unwanted but irreversible side effects.
The limited ability of adult stem cells to form many tissues, however, may be an advantage. “Adult stem cells have been used for years without side effects of that type,” said Daniel Marshak, vice president of bioscience research and development for East Rutherford, NJ-based Cambrex, which provides services to stem cell scientists. “The adult stem cell has somewhat less capacity to do what it wants, but it may be somewhat more programmed to do the right thing.”