Stem Cells Taken From Adults and Reprogrammed May Be Rejected as Foreigners

By Valerie Ross | May 14, 2011 5:15 pm

Mouse embyronic stem cells

What’s the News: Reprogrammed stem cells—cells taken from an adult and turned back into stem cells—can be rejected by the body, at least in mice, suggests a new Nature study. Donated tissues and organs are often attacked by a patient’s immune system, since reprogrammed stem cells can be made from a patient’s own skin, researchers had hoped these cells offered a way to avoid such rejection by letting patients, in essence, donate tissue to themselves. But the new finding may be a significant setback to what is a promising line of treatment.

How the Heck:

  • Researchers took embryonic stem cells and reprogrammed stem cells—called induced pluripotent stem cells, or iPS cells—from two strains of mice. The mice in each strain were genetically identical to each other, so that mice within a strain would essentially recognize each other’s cells as their own.
  • As expected, mice rejected embryonic stem cells from the other strain, but not from their own strain. Embryonic stem cells from their own strain grew and formed teratomas, clumps of differentiating tissues that are a sign the stem cells are doing well and able to form various adult tissues.
  • When the researchers injected mice with iPS cells from their own strain, few teratomas formed, and those that did were quickly rejected, much as though they’d been stem cells from the other strain.

What’s the Context:

  • iPS cells were thought to have two primary advantages over embryonic stem cells: They didn’t require the destruction of human embryos, thus circumventing those legal and ethical issues, and they could be genetically tailored to individual patients.
  • This was the first study to directly test whether the immune system would attack iPS cells.
  • It is not, however, the first problem with iPS cells that research has revealed. These stem cells sometimes retain epigentic traces of their past identities and are often riddled with errors in their genetic code, both of which could keep the cell from becoming a fully functional unit of a new tissue.
  • The fact that iPS cells can be rejected raises major questions about their treatment potential. “The path to the clinic just got a whole lot murkier,” stem cell researcher Robert Lanza told the New York Times.

Not So Fast:

Reference: Tongbiao Zhao, Zhen-Ning Zhang, Zhili Rong, & Yang Xu. “Immunogenicity of induced pluripotent stem cells.” Nature, published online May 13, 2011. DOI: 10.1038/nature10135

Image: National Science Foundation

CATEGORIZED UNDER: Health & Medicine, Top Posts
  • Paul Knoepfler

    It is very possible that the context of this experiment–namely measuring immune response to teratoma (a type of tumor)–may have contributed in a major way to the finding of immune rejection of the iPS cells. Tumors, even those not made from iPS cells, express abnormal antigens. I’m hopeful that the “normal” differentiated tissues or cells made from iPS cells may be able to fly under the radar of the immune system. We’ll see soon. Stayed tuned! We discuss all this stuff on my lab’s blog . I’m a stem cell researcher.

  • Don Margolis

    In my early writing days I learned that no matter how good the article is, editors write headlines. This headline is typically misleading for stem cell articles written in North America. STEM cells are not reprogrammed, SKIN cells are used to create iPSC.

    Given the huge publicity (for political and financial reasons) given to this silly effort, it is not surprising that researchers such as the first respondent ignore the impossibility of their task. After all, research funds are not that easy to come by, and any research is better than none!

    Let us see why “silly.” The project is to create a new, never before seen stem cell which can emulate the presumed ability of ESC to be pluripotent, i.e. to become any type of cell it wants to be. That statement alone is false, since no ESC wants to become anything but a fetus.

    Yes, the ESC can be trained to become a desired cell, but when its real goal is denied, it gets cranky and tends to create tumors. It also, after a decade of research, still triggers an immune response which no one has begun to solve. Failed ESC researchers (that means 100% of them) then slink into a corner and mutter “immune suppressive drugs,” never mentioning the price that the victim, errr patient, pays for seriously weakening his immune system.

    So the real task for the iPSC researcher is to create a new type of stem cell which is “embryonic-like” but has none of the four huge ESC negatives: (1)Immune Response (2)Tumors, (3)Creating Mutant Tissue, (4)Outrageous Costs, all of which have been ignored in the four years of nonsense iPSC publicity until this new finding. Not only has four years failed to uncover the beginnings of a solution, but until today they failed to even define the problem!

    Finally, this fine article crashes with the last statement, “Not so Fast.” Not only must this fantasy stem cell not be rejected, dear writer, but it must not cause tumors. Also, it must not create mutants, as proven it does earlier this year. And it must not cost tens of thousands of dollars per patient just to create it.

    None of this effort was ever meant to help patients, rather the whole ESC project exists to avoid informing a kept-ignorant public about the only stem cells ever to improve lives, ASC, which virtually every misinformed MD in North America tells his inquiring patients “They don’t work,” despite 1500+ successful ASC clinical trials (completed or ongoing) and 10,000+ patients walking around enjoying improved lives!
    Don Margolis, Chairman
    Repair Stem Cell Institute

  • ets_spoon

    I take it ASC stands for Adult Stem Cell . . . Valerie, maybe you could interview this Margolis character; he seems to have some things to say and judging by his e-signature, he feels he is qualified on the topic.

  • Irv Arons

    It really depends on where the iPSCs are implanted. As I will explain in a posting to be made in my online Journal later tonight, iPSCs-derived retinal structures implanted in the mouse eye (an immune priveleged body) by researchers at the Schepens Eye Research Institute created new working retinal tissue, without an immune response.

    Look for Stem Cells in Ophthalmology Update 7: Research Studies with Induced Pluripotent Stem Cells Suggest Opposite Results that I will post online later tonight.

    Irv Arons
    Irv Arons’ Journal

  • Irv Arons

    My Update has now been posted. The link is

    Irv Arons

  • Matt B.

    Don Margolis has a point about the title of the article, but a stem cell is not a zygote. It doesn’t want to become a whole fetus, it wants to become part of one, possibly only one type of tissue.

  • Nyce

    Despite what Margolis has stated, it is possible to take stem cells (such as mesenchymal stem cells) and reprogram them to a less differentiated state (ES-like cells). For example, this paper published in Plos ONE out of Japan

    Skin cells are definitely not the only source for iPS. For someone involved in a stem cell research institute and pushing ASCs, he should take some time to get caught up on what real researchers are doing.

  • PhDinTheProcess

    Instead of bashing what these scientists are trying to do, why not focus discussion instead on the anomalies they observe in iPSCs? Wouldn’t that do considerably more for furthering scientific understanding and discovering, which in turn facilitates medical advancement? Perhaps by working together as a scientific COMMUNITY instead of by functioning under neanderthal-like Watson-and-Crick-type philosophies we could actually make advances in this field, a field from which every single one of us potentially stands to benefit.


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