‘Ethical’ Stem Cell Abnormalities Could Hinder Research

Induced pluripotent stem cells (iPSCs) generated by reprogramming differentiated adult cells are often touted as an “ethical” alternative to embryonic stem cells for applications in regenerative medicine. But research is showing that these cells can have abnormalities that might hinder their eventual clinical development. Two papers in Nature report that techniques for reprogramming fibroblasts into iPSCs cause a 10-fold increase in point mutations and a swell of copy number variations in which sections of DNA are aberrantly repeated (DOI: 10.1038/nature09805 and 10.1038/nature09871). These findings add to three other papers published in recent months reporting potential problems with iPSCs, including chromosomal abnormalities such as trisomies, a common example of which is Down syndrome, as well as incorrect epigenetic marks (Cell Stem Cell, DOI: 10.1016/j.stem.2010.07.017 and 10.1016/j.stem.2010.12.003; Nature, DOI: 10.1038/nature09798). These studies “raise concerns over the implications of such aberrations for future applications of iPSCs,” stem cell researcher Martin F. Pera of the University of Southern California writes in a Nature commentary. Figuring out precisely what in the reprogramming methods causes the genetic and epigenetic abnormalities could permit researchers to find better routes to iPSCs.