More broadly, it remains to be established whether the appearance of such mutations during cell preparation reflects a predisposition to mutation by the hiPSCs, whether during or after reprogramming. If so, despite the low probability that random mutations – if they are indeed few and random – would prove tumorigenic, the appearance of mutations with iPSC induction and differentiation could pose a significant challenge to the therapeutic development of this cell source. As a result, one might posit that hESC-derived phenotypes, rather than iPSC-derived, may be the first into the clinic for a broad variety of disease targets, pending the more rigorous assessments that may be needed to assure the safety of iPSC derivatives.
