Stem cell setback: mice reject their own reprogrammed cells

Induced pluripotent stem cells are made from a patient's own tissue. As such, they shouldn't be attacked by the immune system after a transplant. Not so, a new study shows.

A promising stem cell treatment suffered an unexpected setback on Friday, when a new study revealed that transplanted, reprogrammed cells triggered a damaging immune response.

Induced pluripotent stem (iPS) cells are derived from a patient’s own tissue. Like embryonic stem cells, iPS cells can grow into many other cell types – an ability called pluripotency – to help replace damaged tissues and organs.

Presumably, a major advantage of using iPS cells is how they’re supposed to avoid the whole immune rejection issue because they’re derived entirely from the patients themselves. (Also, since iPS cells don’t require embryo use, they’re not subject to federal restrictions like embryonic stem cells.)

To make iPS cells, scientists use a technique called cellular reprogramming, ScienceNOW explains. By activating a handful of genes, they turn the developmental clock backward in adult cells, converting them into an embryo-like state.

Now, Yang Xu and colleagues from UC San Diego show how mice have rejected their transplanted iPS cells.

The team made the cells by reprogramming skin cells. Then they transplanted those into mice that are genetically identical as the donors. This mimics transplantation of cells from one person back into the same person. Nature News reports:

When transplanted, the embryonic stem cells gave rise to teratomas – tumors 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 immune response was the same as that triggered by an organ transplant between individuals. According to the chief scientific officer of Advanced Cell Technology: “The path to the clinic has just gotten a lot murkier.”

Xu’s next steps will be to examine which specific cells in the teratomas trigger immune rejection and under what conditions. Perhaps the reprogramming methods can be fine-tuned to avoid the problem altogether.

"It's important to continue pursuing treatments based on human embryonic stem cells," says Xu, "as these have so far proved to be the most reliable and versatile for regenerating new cells and tissue."

The study was published in Nature last week.

Image: an infiltration of immune cells (dark brown) in the tissues formed by iPSCs / Yang Xu, UCSD

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