FEAR OF REJECTION: Stanford researchers report that if human embryonic stem cells are transplanted into a person, the recipient's immune system will likely kill them within a week.
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The much-ballyhooed human embryonic stem cell apparently may share a problem with transplanted organs: a high probability of rejection.

Researchers at Stanford University School of Medicine found that mice mounted an immune response after being injected with human embryonic stem cells (hESCs). The result: all the transplanted stem cells—which hold the promise of maturing into several different types of tissue—were dead within a week.

Wu says that the fact that the hESCs could not survive in the mouse, coupled with previous work showing that the animals also reject mice ESCs, suggests that if human stem cells were transplanted to a patient, they would very likely provoke an immune response. The U.S. Food and Drug Administration, however, has not approved the injection of hESCs into patients because the raw cells have the potential to become cancerous.

According to Stanford radiologist Joseph Wu, co-author of a study appearing in Proceedings of the National Academy of Sciences USA, the study tells scientists that such cells do not slip under the radar of our immune systems. Some scientists had believed they did, because an embryo is "foreign" to a mother. After all, half of its genes—and therefore some percentage of its protein makeup—are from the father.

The new study not only showed that these cells are not invisible to the immune system, but using a noninvasive molecular imaging technique, the scientists could see when exactly the cells were dying off. The finding means that people who may one day be treated using pools of stem cells taken from many lines could reject them, making the therapy useless.

"[This result is] not a disappointment, it's more of a reality check," Wu says. "I think there's some promise [to hESCs], but you don't want to be foolish and say these cells are going to cure things in the next five years."

When Wu and his team took hESCs and injected them into the legs of mice with compromised immune systems, the cells thrived and multiplied. In mice with functioning immune systems, however, the cells began to die within a week and were completely gone after 10 days. When the researchers tried to inject more stem cells into the mice, their immune systems remembered the foreign invaders, and the cells fared worse—dying in two to four days.

The Stanford team noted that the immune reaction was similar to rejections during organ transplantation. So, the group repeated the experiment in animals that received two common antirejection medications—tacrolimus and sirolimus—which they hoped would suppress their immune systems enough to let the stem cells thrive. They lasted up to 28 days.

But, is that enough time for them to have a therapeutic effect?

"We don't know if that's long enough for them to mature and have an effect," Wu says. "Our only finding here is that this combo of drugs can have a medicating effect on these cells"—allowing them to survive longer.

Leslie Silberstein, program leader for cell therapy at the Harvard Stem Cell Institute, called the new findings important, but said he was not surprised to find that human ESCs were attacked in the same way as other cells.