Induced pluripotent stem cells rejected by mouse immune system

A recent paper in the journal Nature by Yang Xu and colleagues from the University of California, San Diego has shown that induced pluripotent stem cells (iPSCs) made from mouse embryonic skin cells made tumors called teratomas when injected into those same mice that were attacked by the mouse’s immune system. This paper has questioned whether iPSCs can be used for therapeutic purposes in human patients.

This conclusion, however, does not necessarily follow. In the first place, this work derived its iPSCs not from mature adult cells, but from embryonic cells. Secondly, the transplanted cells were not differentiated cells, but were stem cells, which are known to form teratomas when transplanted into laboratory animals. Because teratomas have the capacity to grow into various tissues, they are invaders. Secondly, they almost certainly express surface proteins that the immune system has never seen before. This would probably induce the immune system to attack the teratoma.

Secondly, many papers have transplanted differentiated iPSCs into rodents with no reports of rejection by the immune system (reviewed in Timothy J. Nelson, “Induced pluripotent stem cells: advances to applications,” Stem Cells and Cloning Stem 3 (2010): 29-37). Surely, this paper represents a non-analogous circumstance that has cast aspersions on a completely different clinical application.

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Professor of Biochemistry at Spring Arbor University (SAU) in Spring Arbor, MI. Have been at SAU since 1999. Author of The Stem Cell Epistles. Before that I was a postdoctoral research fellow at the University of Pennsylvania in Philadelphia, PA (1997-1999), and Sussex University, Falmer, UK (1994-1997). I studied Cell and Developmental Biology at UC Irvine (PhD 1994), and Microbiology at UC Davis (MA 1986, BS 1984).

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