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A Possible Setback for Reprogrammed Stem Cells

In mice, stem cells derived from adult tissue can trigger immune rejection, even when matched to the tissue donor.

A promising type of stem cell may not be as well-suited for tissue replacement transplants as scientists had hoped. According to new research published in Nature, induced pluripotent stem (iPS) cells—which are derived from adult tissue but, like embryonic stem cells, have the potential to proliferate indefinitely and to turn into any type of tissue—trigger an immune reaction when the undifferentiated cells are transplanted into tissue-matched mice.

However, the significance of the finding is not yet clear. Researchers have only studied cells from mice, and human iPS cells may not trigger the same reaction. In addition, most stem cell-based therapies would involve transplantation of differentiated cells, such as brain cells or liver cells, which might not provoke the immune system.

IPS cells, first derived in 2007, elicited excitement among the regenerative medicine field because they could theoretically be made from skin cells from any patient, generating genetically matched cells that would presumably not trigger an immune reaction. (Cell transplants from a non-matched donor require the recipient take immune-suppressing drugs.)

Researchers from the University of California, San Diego, tested the theory by creating both embryonic stem cells and iPS cells from mice and then transplanting the cells into genetically identical mice. The animals’ immune system attacked the iPS cells but not the embryonic stem cells.

According to an article in Nature;

When transplanted, the embryonic stem cells gave rise to teratomas — tumours containing a chaotic jumble of cell types, which are used as a signifier of a cell’s pluripotency. Most of the iPS cells, by contrast, were not able to form teratomas, or made teratomas that were attacked or rejected by the immune systems of the host mice.

… The team found that certain genes were expressed at much higher levels in the teratomas formed by iPS cells than in those formed by embryonic stem cells. Two of the genes — Zg16 and Hormad1 — were specifically targeted in immune attacks. Xu suggests that these genes are normally turned off by the time a fetus begins the process of developing immune tolerance to its own tissues, so they are not recognized as ‘self’ by the host’s body; the iPS reprogramming procedure might alter the normal expression of these genes.

IPS cells are currently being used to screen drugs and study disease; scientists have developed cell lines from people with different disorders, such as Parkinson’s. They then differentiate the cells into the cell type damaged in the disease and search for the underlying molecular flaws. Researchers emphasize that iPS cells still relatively little studied compared to embryonic stem cells, and extesnvie research is needed before using them in therapies. Another recent study, for example, showed that iPS cells seem to have more genetic abnormalities than embryonic stem cells.

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