1. Graft survival of major histocompatibility complex deficient stem cell-derived retinal cells
- Author
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Masaaki Ishida, Tomohiro Masuda, Noriko Sakai, Yoko Nakai-Futatsugi, Hiroyuki Kamao, Takashi Shiina, Masayo Takahashi, and Sunao Sugita
- Subjects
Medicine - Abstract
Abstract Background Gene editing of immunomodulating molecules is a potential transplantation strategy to control immune rejection. As we noticed the successful transplantation of retinal pigment epithelium (RPE) derived from embryonic stem cells of a cynomolgus monkey that accidentally lacked MHC class II (MHC-II) molecules, we hypothesized immune rejection could be evaded by suppressing MHC-II. Methods Gene editing by the Crispr/Cas9 system was performed in induced pluripotent stem cells derived from a cynomolgus monkey (miPSCs) for targeted deletion of the gene coding class II MHC trans-activator (CIITA). Then the CIITA-knocked out miPSCs were differentiated into RPE cells to generate miPSC-derived MHC-II knockout RPE. The MHC-II knockout or wild-type RPEs were transplanted into the eyes of healthy cynomolgus monkeys. All monkeys used in this study were male. Results Here we show when MHC-II knockout RPE are transplanted into monkey eyes, they show suppressed immunogenicity with no infiltration of inflammatory cells, leading to successful engraftment. Conclusions Our results reasonably evidence the efficacy of MHC-II knockout iPSC-RPE transplants for clinical application.
- Published
- 2024
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