Body attacks lab-made stem cells

In mice, the immune system targets and destroys reprogrammed adult skin cells

Stem cells created in the lab by reprogramming adult cells from a patient’s own body can come under attack from the immune system, a new study in mice suggests.

EARLY REJECTION T cells (brown) creep into tissues generated by reprogrammed stem cells (blue). This infiltration is the start of the type of tissue rejection seen in transplants. Y. Xu/UC San Diego

The finding may present a major barrier to using reprogrammed stem cells, called induced pluripotent stem cells or iPS cells, in treatments to repair or replace damaged tissues.

The study introduces a needed note of caution into what had become a headlong race to rush reprogrammed cells into clinical use, says Chad Tang, a stem cell biologist at Stanford University who was not involved in the new work. “The iPS cell phenomenon is so new and so hyped up that it’s good we’re taking a step back to ask what they can really do.”

Because reprogrammed cells are derived from a patient’s own cells, most researchers had assumed that the immune system would not reject the cells as it does those from another person.

But researchers from the University of California, San Diego, found that reprogrammed stem cells transplanted into genetically identical mice were killed in the same sort of immune attack that occurs during the rejection of transplanted organs. iPS cells reprogrammed using viruses provoked a more intense immune reaction than ones created using a virus-free method, the researchers report online May 13 in Nature. Embryonic stem cells put into similar mice were not rejected.

Immune cells called T cells led the attack on the reprogrammed stem cells, which were derived from skin cells. The T cells keyed in on certain proteins made in some of the reprogrammed cells. Reprogrammed cells that didn’t produce those proteins appeared to be safe from attack.

The researchers don’t yet know if stem cells reprogrammed from other types of tissues would prompt the same immune onslaught as those created from skin cells do, says UCSD’s Yang Xu. If rejection is limited only to certain types of reprogrammed cells, then some others may be used safely. But if the problem is more widespread, researchers may have to rethink the goal of transplanting the cells into patients. “It’s hard to say how big the hurdle is,” Xu says.

Improving the reprogramming method to make iPS cells more like embryonic stem cells may solve the problem, Xu says. Recently, other groups have shown that reprogrammed cells retain molecular memories of their former identities and aren’t clean slates that can morph into any cell type the way embryonic stem cells can (SN: 8/14/10, p. 15).

Tina Hesman Saey is the senior staff writer and reports on molecular biology. She has a Ph.D. in molecular genetics from Washington University in St. Louis and a master’s degree in science journalism from Boston University.

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