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Thread: Body's immune system rejects transplanted human embryonic stem cells

  1. #1

    Body's immune system rejects transplanted human embryonic stem cells

    This is a significant issue for Geron and others who are claiming that non HLA-matched hESC will not be immune rejected when transplanted into the spinal cord. This has been our experience as well.

    http://www.sciam.com/article.cfm?id=...lls&ec=su_stem


    August 19, 2008 in Biology | 9 comments | Post a comment
    Body May Reject Transplanted Human Embryonic Stem Cells
    Finding suggests that embryonic stem cell therapy could encounter the same problems organ transplants do

    By Nikhil Swaminathan

    embryonic stem cells

    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.

    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.

  2. #2
    Quote Originally Posted by Geron 7/5/06
    Data show that human immune cells have little direct immunoreactivity with GRNOPC1. These findings suggest that temporary, low–dose immune suppression should enable transplanted GRNOPC1 to survive without immune rejection. When the injury heals, the transplanted cells should be protected by the blood–brain barrier, allowing immunosuppression to be withdrawn.
    http://www.geron.com/media/pressview.aspx?id=765

  3. #3
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    Question

    Not derived cells? How can hESC just like that cure SCI? I though there was a consensus that this couldn't work in any cases.
    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.
    And died within a week too. These survied long enough though...
    Paralyzed animals transplanted with EBD cells partially recovered motor function 12 and 24 weeks after transplantation, whereas control animals remained paralyzed.

    <sci>

    We conclude that cells derived from human pluripotent stem cells have the capacity to restore neurologic function in animals with diffuse motor neuron disease via enhancement of host neuron survival and function.

    http://www.ncbi.nlm.nih.gov/pubmed/12832537

  4. #4
    Hmmm. I thought this wouldn't even be a question. LIke it was a given. Just like any other transplant of organ or tissue the immune system will reject it unless on certain medication. But don't they have a way around this? Like getting stem cells from bone marrow or olfactory stem cells and even getting them from the skin?

  5. #5
    Quote Originally Posted by XYNaPSE
    But don't they have a way around this? Like getting stem cells from bone marrow or olfactory stem cells and even getting them from the skin?
    They do.

    Tom Okarma from Geron says that they'll be able to overcome this by tolerizing (see "To 4") the body with dendritic cells so the hESCs won't be rejected.
    ...it's worse than we thought. it turns out the people at the white house are not secret muslims, they're nerds.

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    So why does not more people advocate for much more basic research instead of going in circles?

  7. #7
    Quote Originally Posted by Leif
    So why does not more people advocate for much more basic research instead of going in circles?
    Assuming you're addressing my iPS favortism, Okarma may be wrong.
    ...it's worse than we thought. it turns out the people at the white house are not secret muslims, they're nerds.

  8. #8
    Quote Originally Posted by Steven Edwards
    Assuming you're addressing my iPS favortism, Okarma may be wrong.
    This is a serious question that requires convincing data because it means whether the patients need to get immunosuppression or not. I know that if we transplant human embryonic stem cells into the spinal cord of rats, the cells are rejected if we do not immune-suppress the rats. So, the claim that the cells are not immune-rejected need to be confirmed and convincing.

    Wise.

  9. #9
    Quote Originally Posted by Wise Young
    This is a serious question that requires convincing data because it means whether the patients need to get immunosuppression or not. I know that if we transplant human embryonic stem cells into the spinal cord of rats, the cells are rejected if we do not immune-suppress the rats. So, the claim that the cells are not immune-rejected need to be confirmed and convincing.

    Wise.
    Doesn't the fact that the CNS is somewhat immune-privileged, with little to no MHC presented on the cell surfaces, make comparing impantation of hESCs into other parts of the body inconsistent. Like comparing apples and oranges. They seem to be very different environments. Plus, hESCs already differentiated into neuronal cell types, like oligodendrocytes and astrocytes, should display low MHC themselves.

    Perhaps the trauma caused by implantation causes up-regulation of MHC expression? And activation of microglia? I do know that the CNS is not as "privileged" as we previously thought.

    But it should be noted that transplanting cells into the CNS should be theoretically "easier" to do given the fact that the CNS already has a natural form of immunosuppression.
    Last edited by walderness; 08-31-2008 at 02:58 PM.

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