Somatic coding mutations in human induced pluripotent stem cells.

Adult stem cells or human induced pluripotent stem (hiPS) cells are generated by expressing defined factors in fibroblast cells from adult patients in a process called reprogramming. These cells have great promise for regenerative medicine as they maintain the genome of the original donor, thus reducing the possibility of immune system rejection in stem cell therapies. One concern with hiPS cells, however, is whether the reprogramming process could introduce genetic modifications, or mutations, in hiPS cells that are not present in the original donor cells. To address this concern, we investigated whether hiPS cells have a high rate of mutation by sequencing the protein coding regions of the hiPS cell genomes and comparing these sequences to the donor fibroblast cells. We sequenced 22 hiPS lines and found that they did, in fact, have more mutations than the parent fibroblasts suggesting that the reprogramming process and subsequent culture steps may not maintain complete genomic integrity. The mutations discovered in these cell lines were more common in genes involved in cancer, although no cell line had the same number of mutations, suggesting that some lines may be more affected than others. Given the tremendous potential of these cells for therapeutic use, it is important to continue research on mutation rates in hiPS, develop rigorous standards to test for genomic integrity, and perform extensive genetic screening on cell lines intended to be used clinically for cell therapy.