New doubts cast on adult stem cell potential

Researchers at Stanford University Medical Center in the US have reported that they failed in attempts to coax adult blood-forming stem cells in mice into forming tissues other than blood and immune cells.

The university said that the research, published in the September 5 issue of Science Express, an advance online publication of the journal Science, struck a blow at the idea that stem cells taken from adults had the same developmental potential as those taken from embryos.

Dr Irving Weissman, the Karel and Avice Beekhuis Professor of Cancer Biology at Stanford and lead author of the study, is a long-time advocate of embryonic stem cells as the only ones with the ability to form all adult tissues.

Weissman and postdoctoral fellow Dr Amy Wagers studied whether stem cells taken from adult mice could integrate into adult tissues. They isolated adult blood-forming stem cells from the bone marrow of mice, and engineered them to make a green fluorescent protein visible under a microscope. The researchers then injected a single stem cell into mice whose bone marrow had been knocked out by irradiation.

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 represented an adult stem cell developing into other tissue types, the level was so low that it would not 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 a statement.

Assoc Prof Paul Simmons, head of the stem cell biology program at Melbourne's Peter MacCallum Cancer Institute, said that research into the plasticity of adult stem cells was "very new".

Simmons, who had not read the paper at time of writing, said that adult stem cell research in this field had been marked by failure to reproduce results from one lab to another. Some of that, he said, was probably due to different groups isolating stem cells on the basis of different markers.

"One of the arguments that opponents of embryonic stem cell research have raised is that you don't need them, as adult stem cells are very plastic," he said. "If plasticity is a phenomenon that cannot be validated by other scientists then this says that adult stem cells are essentially restricted, not pluripotent."

He said that this would not allow the sustainability of the argument by opponents of embryonic stem cell (ES cell) research that adult stem cells could do everything that ES cells could.

Weissman said the study was the first time anybody had injected a single adult stem cell and showed that it made only blood. He said the research should teach other researchers and others to wait for all the data before they rushed to judgment, "especially when you are jumping to a political judgment that has big policy repercussions."

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 she hoped the research would temper the enthusiasm for stem cell plasticity. "Maybe it's not the answer it appeared to be," she said.