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Abstract #95130 Published in IGR 22-2
Transplantation of reprogrammed peripheral blood cells differentiates into retinal ganglion cells in the mouse eye with NMDA-induced injury
Zhou X; Rui Y; Peng J; Wang Y; He Y; Wang C; Peng M; Zhang X; Xia X; Song WJournal of Cellular Physiology 2021; 236: 8099-8109
The generation of patient-specific induced pluripotent stem cells (iPSCs) holds significant implications for replacement therapy in treating optic neuropathies such as glaucoma. Stem-cell-based therapy targeted at replacing and replenishing retinal ganglion cells is progressing at a fast pace. However, clinical application necessitates an efficient and robust approach for cell manufacturing. Here, we examine whether the embryo body derived from human peripheral blood-derived iPSC can localize into the host retina and differentiate into retinal ganglion cells after transplantation into a glaucoma injury model. Human peripheral blood T cells were isolated and reprogrammed into an induced pluripotent stem cell (TiPSC) line using Sendai virus transduction carrying transcription factors Sox2, Klf4, c-Myc, and Oct4. TiPSCs were differentiated into RGC using neural basal culture. For in vivo studies, embryo bodies derived from TiPSCs (TiPSC-EB) were injected into the vitreous cavity of N-Methyl-d-aspartic acid (NMDA)-treated mice 2 weeks before sacrifice and retinal dissection. Induced pluripotent stem cells generated from human peripheral blood T cells display stem cell morphology and pluripotency markers. Furthermore, RGC-like cells differentiated from TiPSC exhibit extending axons and RGC marker TUJ1. When transplanted intravitreally into NMDA-treated mice, embryo bodies derived from TiPSC survived, migrated, and incorporated into the retina's GCL layer. In addition, TiPSC-EB transplants were able to differentiate into TUJ1 positive RGC-like cells. Retinal ganglion cells can be differentiated using human peripheral blood cells derived iPSC. Transplantation of embryo body derived from TiPSCs into a glaucoma mouse model could incorporate into host GCL and differentiate into RGC-like cells.
Hunan Key Laboratory of Ophthalmology, Eye Center of Xiangya Hospital, Central South University, Changsha, Hunan, China.
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