Alternate Sources of RPCs
generation of chimeric embryo and RGCs using the iPS cells derived by non-nucleic acid methodAlternate Sources for RPCs and Regeneration by Rejuvenation: While progenitors isolated from the embryonic retina shed valuable light on the regulatory mechanisms their use in cell therapy for degenerative blinding diseases is rather impractical for ethical and immunological reasons. Therefore, we are interested in renewable alternate sources for RPCs and we demonstrated the retinal potential of progenitors derived from the ciliary epithelium, limbal epithelium, ES and iPS cells. Towards our goal of stem cells for ex-vivo cell therapy and establishing disease models, we demonstrated that somatic stem cells (e.g., limbal stem cells) can be reprogrammed into pluripotent stem cells by a non-nucleic acid method by the simple exposure to ES cell conditioned medium, circumventing the risk of insertional mutagenesis, associated with the nucleic-acid approach to reprogramming. The rejuvenated stem cells with pluripotency are robust source of RPCs, which could be directly differentiated along photoreceptors and RGC lineages. Currently, we are developing a xeno-free small molecule-based strategy to generate RGCs from human ES and iPS cells with high efficiency and stable phenotype. The de novo generated RGCs share properties with the native RGCs at genomic, biochemical, cellular and functional levels. We are using this rejuvenation strategy by recapitulation of early development toward regeneration and/or rescue of diseased RGCs and photoreceptors.  The figure shows the generation of chimeric embryo and RGCs using the iPS cells derived by non-nucleic acid method (image: Sowmya Parameswaran).