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.

9 Comments

1. 1. chazwatson 08:38 PM 8/19/08

   It seems intuitive that stem cells implanted from a different species are more likely to be rejected than those from the same species. The article doesn't finish with any reasons why human stems cells placed within a human could be rejected, which is the bold conclusion written in the photo's caption.

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2. 2. aaronic_abacus in reply to chazwatson 09:53 PM 8/19/08

   What about cloned embryonic stem cells using the patients dna?

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3. 3. darkunknown 11:27 PM 8/19/08

   do these cells belong to the patient?

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4. 4. darkunknown 11:31 PM 8/19/08

   ok now i get it. -.-
   have they tried mESCs (mouse embryonic stem cells)?
   
   i they should be trying to find out why an embryo is not rejected by its mother instead of assuming it works for all hESCs.

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5. 5. darkunknown 11:34 PM 8/19/08

   ok now i get it. have they tried mESCs (mouse embryonic stem cells)? i would think that a body part of a person is not welcomed by a mouse?
   
   should they be trying to find out why embryos are not rejected by their mother instead of assuming that it works for all hESCs? or do they know that already?
   
   

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6. 6. aaronic_abacus 02:27 AM 8/20/08

   Using cloned steam cells would help the patients accept the transplant, the best donar is family or even better a twin. A clone is a identical twin.

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7. 7. chazmania 06:06 AM 8/20/08

   I would not have expect such a respectable periodical as SciAm to be take sides in the ethical debate on human embryonic stem cells. I was surprised when Nikhil Swaminathan wrote "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." It is scientifically incorrect to call cells that could be teratogenic and produce self-limiting growths cancerous. This is either sloppy writing or be being biased.
   

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8. 8. halpinde 04:05 PM 8/22/08

   This is not really very newsworthy at all. This has been the consensus of the majority of hESC researchers for years. All previous attempts have failed similarly; that is why there is so much effort being put into induced pluripotent stem cells and genetically modified hESCs. By creating a large bank of hESC lines, which could be modified to be less immunogenic (e.g. HLA homozygous), a match could be found for nearly everyone in a fashion similar to how organ transplants are matched up today. Beyond that, though, the idea of using patient-specific iPS cells would completely eliminate the issue of rejection. And in the meantime, the immune-privileged status of the central nervous system means that rejection issues may not be a serious problem for therapies there, some of which may be beginning clinical trials soon: http://www.geron.com/products/productinformation/spinalcordinjury.aspx
   
   Still, they're right to say that it will take more than 5 years to see serious therapeutic applications living up to the full promise of hESCs, although primarily for a number of reasons beyond immune system compatibility.

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9. 9. Jofez 11:12 PM 8/25/08

   Everyone has a different chemical make up, so this treatment won't have an effect for everybody.

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