This study was designed to determine whether adult mouse induced pluripotent stem cells (iPSCs), could be used to produce retinal photoreceptor precursor cells that could be used for retinal transplantation to restore retinal function in retinal degenerative hosts. iPSCs were generated using adult dsRed mouse dermal fibroblasts via retroviral induction of the transcription factors Oct4, Sox2, KLF4 and c-Myc. As with normal mouse embryonic stem cells, adult dsRed iPSCs were shown to be both pluripotent (ability to make any tissue in the body) and had an unlimited capacity for self-renewal, both of which are characteristics of stem cells. Following differentiation, a large proportion of the cells expressed retinal progenitor cell markers and went on to express photoreceptor markers. When tested using calcium imaging these cells were shown to exhibit characteristics of normal retinal physiology, responding to delivery of neurotransmitters. Following subretinal transplantation into degenerative hosts, differentiated iPSCs took up residence in the retinal outer nuclear layer and gave rise to increased electro retinal function as determined by ERG and functional anatomy. As such, adult fibroblast-derived iPSCs provide a viable source for the production of retinal precursors to be used for autologous transplantation and treatment of retinal degenerative disease.
Transplantation of Adult Mouse iPS Cell-Derived Photoreceptor Precursors Restores Retinal Structure and Function in Degenerative Mice
April 29th, 2011