Controversy doesn't derail stem cell progress

Almost unnoticed amid the revival of stem cell politics this year, progress and peril in the science behind the controversy continues to hum along.

Human embryonic stem cells, with their ability to turn into every kind of organ tissue in the body, have tantalized biomedical researchers ever since their 1998 isolation by University of Wisconsin scientists. Organ replacement tissues free from immune system rejection, grown from embryonic stem cells or from more recently discovered "induced" stem cells grown from skin cells, have been envisioned for a decade.

"At this moment, the full promise of stem cell research remains unknown, and it should not be overstated," President Obama said in March while announcing a lifting of the previous administration's restrictions of federal funding on human embryonic stem cell research. He added, "Scientists believe these tiny cells may have the potential to help us understand, and possibly cure, some of our most devastating diseases and conditions."

In a study in the current Nature journal, a team led by George Daley of Children's Hospital Boston offered fresh insight into reaching that goal, demonstrating a novel, purely physical way to make stem cells turn into, or "differentiate" into, blood cells. Without using chemicals to trigger differentiation, the usual approach, the team placed mouse embryonic stem cells into a rotating "flow device," essentially between the inner ring and outer ring of a record-player. The viscous flow, or shear stress, on the cells caused by rotating the rings at different speeds for two days triggered the transformation from unspecialized stem cell to blood cell.

"By itself, the shear stress did it," said study team member William Lensch, in an interview conducted while we were both changing planes last week at Boston's Logan Airport (a small world, science reporting). "We tried all sorts of ways to push a flow along on the cells and they all gummed up, until the rotation method."

Shear flow alone on the cells triggered a jump in the expression of a blood cell gene and blood cell chemicals and limited the stem cells' production of nitric acid, which blocks their differentiation. "Collectively, these data reveal a critical role for biomechanical forces in haematopoietic (blood cell) development," says the study.

Whether similar physical forces play a role in the differentiation of other organ tissues is an open question, Lensch says.

However, other papers out last week say some even more fundamental questions remain.

"The link between stem and tumor cells in science is a very old one," says Paul Knoepfler of the University of California Davis School of Medicine in the current Stem Cell journal. But no one talks about it much, he adds, even though understanding the link remains "an essential bridge to cross along the way" in someday turning embryonic cells into organ transplants.

After all, the most basic test of whether stem cells are truly "pluripotent" or able to turn into any type of tissue in signature embryonic cell fashion, Knoepfler says, is to inject them into a mouse and see if they grow into tumors. "Why would (embryonic stem cells), supposedly normal counterparts to (cancer cells), also have the ability to cause tumors?" he asks. "The simplest but most troublesome answer is that (embryonic stem cells and cancer cells) are in fact, as was originally assumed, quite similar types of cells."

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