Many investigators have shifted their efforts in cell therapeutic development to iPSCs, to capitalize upon the potential for autologous therapy using patient-derived cells, whether with or without genetic correction of any underlying mutations. Yet despite the attractiveness of iPS cell sources, use of these cells is not without risk. The transcription factor-induced reprogramming of somatic cells into fibroblasts can be an imperfect process, with both incomplete reprogramming to stem cell ground state, and retention of epigenetic marks referable to donor cell phenotype (Hochedlinger and Plath, 2009; Kim et al., 2010; Polo et al., 2010). The induction process may also be associated with reprogramming-associated mutations (Gore et al., 2011; Sugiura et al., 2014), which though poorly understood, have already necessitated the halt of one clinical trial, of iPSC-derived retinal pigment epithelial transplants as noted previously.
