Nat. Biotech. https://doi.org/10.1038/s41587-019-0227-7 (2019)

Full realization of the therapeutic promise of induced pluripotent stem cells (iPSCs) will require that they be immunologically tolerated by the recipient; however, even autologous iPSCs can sometimes elicit an immune response. In Nature Biotechnology, Schrepfer and colleagues assess the mutation rates of mitochondrial DNA (mtDNA) in both mouse cells and human cells undergoing reprogramming to iPSCs. mtDNA is known to have less-reliable repair mechanisms, and indeed the investigators observe that the number of non-synonymous mutations in the mtDNA of iPSCs is directly related to the number of in vitro passages. These mtDNA mutations can generate neoantigens able to stimulate immune responses and immunological rejection. These findings reveal a mechanism that underpins the loss of autologous iPSC immunological silence and suggest that screening of mtDNA may be important.