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of MSCs impede their mass production and quality control. Induced pluripotent stem cell (iPSC)-derived MSCs (iMSCs) can be infinitely expanded, providing advantages over conventional MSCs in terms of meeting unmet clinical demands. Methods: The potential of MSC therapy for Leber\u2019s hereditary optic neuropathy (LHON) remains uncertain. In this study, we used HLA-homozygous induced pluripotent stem cells to generate iMSCs using a defined protocol, and we examined their therapeutic potential in rotenone-induced LHON-like models in vitro and in vivo. Results: The iMSCs did not cause any tumorigenic incidence or inflammation-related lesions after intravitreal transplantation, and they remained viable for at least nine days in the mouse recipient\u2019s eyes. In addition, iMSCs exhibited significant efficacy in safeguarding retinal ganglion cells (RGCs) from rotenone-induced cytotoxicity in vitro, and they ameliorated CGL+IPL layer thinning and RGC loss in vivo. Optical coherence tomography (OCT) and an electroretinogram demonstrated that iMSCs not only prevented RGC loss and impairments to the retinal architecture, but they also improved retinal electrophysiology performance. Conclusion: The generation of iMSCs via the HLA homozygosity of iPSCs offers a compelling avenue for overcoming the current limitations of MSC-based therapies. The results underscore the potential of iMSCs when addressing retinal disorders, and they highlight their clinical significance, offering renewed hope for individuals affected by LHON and other inherited retinal conditions.<\/jats:p>","DOI":"10.3390\/cells12222617","type":"journal-article","created":{"date-parts":[[2023,11,13]],"date-time":"2023-11-13T02:10:43Z","timestamp":1699841443000},"page":"2617","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["HLA-Homozygous iPSC-Derived Mesenchymal Stem Cells Rescue Rotenone-Induced Experimental Leber\u2019s Hereditary Optic Neuropathy-like Models In Vitro and In Vivo"],"prefix":"10.3390","volume":"12","author":[{"given":"En-Tung","family":"Tsai","sequence":"first","affiliation":[{"name":"Institute of Clinical Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei 112201, Taiwan"},{"name":"Department of Medical Research, Taipei Veterans General 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