Induced pluripotent stem cells promote retinal ganglion cell survival after transplant

Abstract

PURPOSE. The purpose of this study was to characterize whether induced pluripotent stem cells (iPSCs) affect survival of grafted retinal ganglion cells (RGCs) after transplantation. METHODS. For in vitro studies, human iPSCs were either directly cocultured with mouse RGCs or plated in hanging inserts in RGC cultures for 1 week. For ex vivo studies, RGCs and iPSCs were seeded onto the inner surface of an adult rat retina explant and cultured for 1 week. For in vivo studies, RGCs and iPSCs were intravitreally coinjected into an adult rat eye 1 week before examining retinas by explant and immunostaining. RESULTS. A dose-dependent increase in RGC survival was observed in RGC-iPSC direct cocultures, and RGC-iPSC indirect cocultures showed a similar RGC protective effect, but to a lesser extent than in direct coculture. Enhanced RGC survival was also identified in RGC-iPSC cotransplantations to adult retinas ex vivo and in vivo. In addition, RGCs with iPSC cotransplantation extended significantly longer neurites than RGC-only transplants. CONCLUSIONS. Human iPSCs promote transplanted RGC survival and neurite extension. This effect may be mediated at least partially through secretion of diffusible neuroprotective factors.