As a result of these relative advantages, retinal cell replacement has been perceived as an especially promising target of CNS cell therapy, with multiple trials underway (Schwartz et al., 2015; Song et al., 2015). Yet the need for caution even with such favorable translational opportunities has already been made clear, by the discovery that hiPSC-derived RPEs prepared for autologous graft had acquired unexpected point mutations during preparation, as revealed by whole genome sequencing of the intended donor RPE cells relative to the fibroblasts from which the patient’s iPSCs were derived. While no clinical complications have been reported in the one patient transplanted before that discovery, the very appearance of mutations prompted the investigators involved to halt further recruitment, until the basis of these mutations could be better established, and the safety of the resultant cells better assured. These events highlight the need for further improvement of reprogramming strategies, while nonetheless emphasizing the power of this technology for autologous therapy once optimized.
