Sep. 6, 2002 STANFORD, Calif. - Researchers at Stanford University Medical Center report that they have tried - and failed - to coax adult blood-forming stem cells in mice into forming tissues other than blood and immune cells. This research, published in the Sept. 5 issue of Science Express, an advance online publication of the journal Science, strikes another blow at the idea that stem cells taken from adults have the same developmental potential as those taken from embryos. This work contributes to a growing debate over the fate of embryonic stem cell research. Several researchers have claimed that stem cells taken from adult bone marrow have the same potential to form all adult tissues as do embryonic stem cells. With that in mind, some policy-makers want to ban embryonic stem cell research in favor of similar research using less controversial adult stem cells.
Irving Weissman, MD, the Karel and Avice Beekhuis Professor of Cancer Biology at Stanford and lead author of the current study, has long argued that only embryonic stem cells have the ability to form all adult tissues. The latest paper reinforces that view.
"This is the first time somebody injected a single adult stem cell and showed that it made only blood," said Weissman, who has served on committees to advise the federal and California governments about embryonic stem cell policies. He added that this research should teach other researchers and members of the lay community to wait for all the data before they rush to judgment. "Especially when you are jumping to a political judgment that has big policy repercussions," he added.
Weissman and postdoctoral fellow Amy Wagers, PhD, studied whether stem cells taken from adult mice could integrate into adult tissues. They first isolated adult blood-forming stem cells from the bone marrow of mice. These cells were engineered to make a green fluorescent protein that's visible under a microscope. The researchers then injected a single stem cell into mice whose bone marrow had been knocked out by irradiation. (Bone marrow produces all blood and immune cells.)
After several weeks, the green fluorescent stem cell had single-handedly repopulated the blood and immune cells of the mice. When the researchers searched through more than 15 million muscle, brain, liver, kidney, gut and lung cells, they found only one brain and seven liver cells that were green under the microscope, indicating that these cells were either formed from the adult stem cell or that one of the stem cell's progeny had fused with the original cell.
Weissman and Wagers said that even if these eight cells represent an adult stem cell developing into other tissue types, the level is so low that it wouldn't be useful as a therapy. "It's not to say that nobody should think about adult stem cell plasticity - of course people should look into it - but it's not as robust as it is claimed to be," Wagers said.
In another set of experiments, the researchers tested whether the single adult stem cell could replace intestinal cells when the intestine was destroyed by radiation. After several weeks new cells had grown to replace those that were lost, but none of the new cells was green under the microscope, meaning the cells did not come from the adult stem cell.
Wagers said this research, in conjunction with recent work from other labs that also failed to verify adult stem cell plasticity, should dim the enthusiasm for pursuing research only in adult stem cells. "I hope it tempers the enthusiasm for adult stem cell plasticity. Maybe it's not the answer that it appeared to be," she said.
Other Stanford researchers who contributed to this study are undergraduate student Richard Sherwood and graduate student Julie Christensen.
Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at http://mednews.stanford.edu.
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