The controversy surrounding stem cell research¿in particular, whether the cells should come from embryonic sources or adult ones¿hinges on what, exactly, cells from the two sources are capable of. Embryonic stem cells, which are more politically contentious because they must be harvested from human embryos, can differentiate into any tissue in the human body. Adult stem cells, although available from less controversial sources, have so far shown less plasticity than their embryonic counterparts. Now the results of two studies published online by the journal Nature provide additional insight into the abilities of both classes of stem cells. The findings further suggest that only by investigating the two kinds of stem cells will it be possible to determine which source will prove most useful in treating a particular disease.
Catherine Verfaillie of the University of Minnesota Stem Cell Institute and her colleagues report that a particular kind of adult stem cell, derived from bone marrow and dubbed a multipotent adult progenitor cell (MAPC), can differentiate into nearly all types of mouse tissue. The scientists injected MAPCs into mice blastocysts (embryos comprised of approximately 100 cells), which were then transferred to foster mothers for gestation. The resultant animals exhibited multiple tissue types, including brain, lung, retina, spleen and skin, attributable to the MAPCs. "Some of the animals are 40 percent derived from the bone marrow stem cells, suggesting that the cells contribute functionally to a number of organs," Verfaillie notes. "This is similar to what one would expect of [embryonic stem] cells." The team next injected MAPCs into a living animal and found that the cells still differentiated into liver, intestine and lung tissue, but overall MAPCs were detected in fewer tissue types than in the blastocyst-injected mice.
Contrary to some recent study results that indicate adult stem cells may merely be fusing with cells already present in the body instead of fully differentiating, the researchers report that they did not co-culture the bone marrow cells with other cell types, thereby ruling out fusion in vitro. Verfaillie cautions, however, that the in vivo experiments are not conclusive with regard to the fusion problem. But so far the MAPCs also have not demonstrated a potential problem of embryonic stem cells: growth of tumors known as teratomas, which contain multiple tissue types.
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In the second published paper, Ronald McKay of the National Institute of Neurological Disorders and Stroke and his colleagues report having successfully cultured embryonic stem cells into dopamine-producing neurons, the type lost in Parkinson's disease. By adding a gene called Nurr1 to stem cells from mice, the scientists made an abundance of dopamine neurons; nearly 80 percent of the cells produced the neurotransmitter. When implanted into rats missing dopamine-producing cells on one side of their brains, the stem-cell-derived neurons made functional connections with surrounding cells. And animals that received neurons containing Nurr1 showed more improvement in their Parkinsonian symptoms than did animals that received embryonic stem cells lacking the gene. Although some Parkinson's patients have shown improvements after receiving experimental transplants of fetal tissue cells into their brains, McKay suggests that treatments based on the new findings could hold even greater promise. Because this technique enables routine access to dopamine-producing neurons, researchers will be able to systematically investigate new ways to make using them safe for future patients, he says.
Both groups advise that potential applications of their recent work remain a long way off and that research studies involving the two stem cell types are not mutually exclusive. According to Verfaillie, studies of adult and embryonic stem cells should proceed in parallel because what is learned about one cell type can help advance research into the other. Natalie DeWitt, a senior editor at Nature, concurs. "While the two papers will no doubt rekindle the debate on the relative merits of embryonic versus adult stem cells," she says, "together they emphasize the outstanding potential of stem cells and the need for continued research in all areas of stem biology."