Stem-cell rejection shocks scientists

In an unexpected setback to efforts to harness a promising new type of stem cell to treat diseases, researchers reported Friday that tissues made from those stem cells might be rejected by a patient's immune system, even though the tissues would be derived from the same patient.

The research involved induced pluripotent stem cells, or iPS cells, which can be made from skin cells and appear to have the characteristics of embryonic stem cells. That means they can theoretically be turned into nerve, heart, liver or other types of cells and transplanted to repair damaged organs.

The initial creation of human iPS cells in 2007 electrified scientists because the cells seemed to have two big advantages over embryonic stem cells:

• They were not controversial, because their creation did not entail the destruction of human embryos.

• Since the stem cells could be made from a particular patient's skin cells, they could be used to make tissues that presumably would not be rejected by that patient's immune system.

The latter assumption was never tested, until now. When Yang Xu, a biologist at the University of California, San Diego, and colleagues did so, they found that iPS cells made from mouse skin cells were rejected by genetically identical mice.

Other scientists said the results, published online Friday in the journal Nature, were surprising.

"The path to the clinic has just gotten a lot murkier," said Dr. Robert Lanza, chief scientific officer of Advanced Cell Technology, a company trying to develop medical treatments using embryonic stem cells and iPS cells.

He said it was not clear the results in mice would hold true for humans, though some other scientists said they assumed they would.

The new report is the latest to take some of the shine off iPS cells. In recent months other researchers reported that the cells are prone to various types of genetic abnormalities.

"As with any new technology, there is always this initial phase of infatuation, and then the reality sets in," said Dr. George Daley, director of the stem-cell transplantation program at Children's Hospital Boston.

Daley said the finding about the immune reactions "happened to be a particularly startling result that I wasn't anticipating."

Still, he added, years of work lie ahead before iPS cells would be ready to use in treating people, so it is too early to be discouraged. Many scientists say iPS cells, for now, will be used to create cells — such as brain cells from someone with Alzheimer's disease — that can be used to study diseases in the laboratory.

Xu, whose research was paid for by the National Institutes of Health and by California's stem-cell program, created embryonic stem cells and iPS cells from an inbred strain of mice and implanted those stem cells into other mice of the same strain.

The mice did not have an immune response to the implanted embryonic stem cells. But their immune systems attacked the implanted iPS cells.

Rudolf Jaenisch, a professor of biology at the Massachusetts Institute of Technology and a founding member of the Whitehead Institute, said that in practice, iPS cells would not be implanted into people. Rather, the stem cells would first be turned into specific types of cells, such as brain cells or heart cells. He said it was unclear whether such differentiated cells would elicit the same immune response as the stem cells did in the mice.

Jeanne Loring, director of the center for regenerative medicine at the Scripps Research Institute, said the new findings would not preclude use of the iPS cells for therapy because immune-suppressing drugs could always be used.

But the potential problem with iPS cells might make some scientists take another look at making patient-specific tissues by creating an embryo from a patient's cell through so-called therapeutic cloning.

That approach, which is not known to have been accomplished using human cells, is controversial because the same technique might also be used to create a baby.

"This reopens the whole need for SCNT, which will be controversial," said Lanza, of Advanced Cell Technology, referring to somatic cell nuclear transfer, the scientific term for cloning. "We had thought we had put that aside with this technology."