Versatile Stem Cells Without The Ethical Baggage?

sciencfe 2007Scientists this week reported that they have isolated a new type of cell from amniotic fluid that has many of the characteristics of embryonic stem (ES) cells without the ethical baggage. But other researchers, although enthusiastic about the work, are questioning just how new these so-called amniotic fluid–derived stem (AFS) cells are and are warning that they don’t eliminate the need for ES cells.

The report, published online 7 January in Nature Biotechnology, seems likely to throw a new twist into this week’s congressional debate over legislation to expand ES cell lines available to federally funded researchers.

Congressional leaders were planning to make a splash by getting both houses to pass once again a measure that was vetoed last year by President George W. Bush. But if this much-touted paper persuades the public there’s a ready alternative to ES cells, “the bill won’t have the impact it would have had,” says bioethicist William Hurlbut of Stanford University in Palo Alto, California. The researchers themselves, led by Anthony Atala of Wake Forest University School of Medicine in Winston-Salem, North Carolina, say that AFS cells, obtained from amniocentesis samples, are no substitute for ES cells. But they see them as a unique type occupying an “intermediate” stage between embryonic and adult stem cells in terms of their versatility.

Several groups have already cultivated specialized tissue types from amniotic stem cells. But Atala insists that AFS cells are “absolutely totally different.” He says they are the only amniotic cells that are “fully undifferentiated” and pluripotent—by which he means capable of giving rise to representatives of all three embryonic germ layers. He concedes, however, that it is still unclear whether AFS cells can give rise to all cell types in the body, as can ES cells.

The team, which includes researchers from Children’s Hospital and Harvard Medical School in Boston, has spent the past 7 years working up their evidence that AFS cells are capable of developing into fat, bone, muscle, nerves, liver, and the lining of blood vessels. They injected human AFS cells that had been coaxed to become neural precursor cells into the brains of newborn mice and found that they dispersed throughout the brains. And cells cultivated in a bonegrowing medium not only produced mineralized calcium and other bone markers but also led to the growth of chunks of bonelike material when cultured on scaffolds and implanted into mice. AFS-derived liver cells secreted urea, a liver-specific function, in test tubes.

Atala said at a press conference that the group has unpublished evidence that the AFS cells can also form blood cells. It has yet to produce pancreatic beta cells, needed to treat diabetes, but Atala says, “so far, we’ve been successful with every cell type we’ve attempted.” Like ES cells, said Atala, the amniotic cells grow rapidly, doubling every 36 hours, and the cell lines are capable of extensive self-renewal without differentiation. Unlike ES cells, they can be readily obtained from amniocentesis without harm to the donor or fetus. And they multiply indefinitely without forming tumors—a big peril with ES cells.

Atala, whose university has applied for a patent on the cell type and the team’s method for isolating them, said that amniotic cells may eventually be used as a repair kit for birth defects. He also predicted that banks of cell lines obtained from 100,000 pregnancies could offer reasonably good tissue matches to 99% of the population. Some scientists are deeply impressed. “I believe … that Dr. Atala’s group has discovered a new stem cell,” says adult stem cell researcher Henry

E. Young of Mercer University School of Medicine in Macon, Georgia.

Atala says AFS cells are the only type distinguished by C-Kit, a germ cell marker not reported in other papers about amniotic stem cells. Nonetheless, Dario Fauza of Children’s Hospital, a pediatric surgeon unconnected with the Atala team who has pioneered in cultivating tissues from amniotic stem cells, says he doubts “whether they have indeed discovered a new stem cell. … I have the distinct impression we’re just giving different names to the same cell.” Ming-Song Tsai, a stem cell researcher at Cathay General Hospital in Taipei, Taiwan, agrees. Atala’s study is “excellent,” he says.

But judging by surface markers and other characteristics, he believes “the cells described in this paper are the same cells” he and colleagues described last year in Biology of Reproduction. In that paper, the scientists reported cultivating “mesenchymal” stem cells from a single amniotic cell that could develop not only into multiple mesenchymal lineages but also into neuronl i ke c e l l s . Tsai, who already has a

U. S . Patent on his method, adds that recently they revealed potential as liver cells.

Tsai predicts that amniotic stem cells may become a valuable tool given their “easy access [and] cultivation” and absence of ethical difficulties. But some researchers are taking a wait-and-see attitude. Harvard stem cell researcher Kevin Eggan is skeptical, especially because the field has been “burned” in recent years by hints of pluripotency in other cell types that haven’t panned out.

–CONSTANCE HOLDEN

Science 2007