Graft survival of major histocompatibility complex deficient stem cell-derived retinal cells.

Autor: Ishida M; Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe, Japan.; Department of Ophthalmology, Toyama University, Toyama, Japan., Masuda T; Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe, Japan.; VC Cell Therapy Inc, Kobe, Japan.; Ritsumeikan University, Research Organization of Science and Technology, Kusatsu, Japan., Sakai N; Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe, Japan.; VC Cell Therapy Inc, Kobe, Japan., Nakai-Futatsugi Y; Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe, Japan. futatsugi@vcct.jp.; VC Cell Therapy Inc, Kobe, Japan. futatsugi@vcct.jp.; Ritsumeikan University, Research Organization of Science and Technology, Kusatsu, Japan. futatsugi@vcct.jp., Kamao H; Department of Ophthalmology, Kawasaki Medical School, Okayama, Japan., Shiina T; Department of Molecular Life Science, Tokai University, School of Medicine, Kanagawa, Isehara, Japan., Takahashi M; Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe, Japan.; Ritsumeikan University, Research Organization of Science and Technology, Kusatsu, Japan.; Kobe City Eye Hospital, Department of Ophthalmology, Kobe, Japan.; Vision Care Inc, Kobe, Japan., Sugita S; Laboratory for Retinal Regeneration, Center for Developmental Biology, RIKEN, Kobe, Japan. sugita@vision-care.jp.; Kobe City Eye Hospital, Department of Ophthalmology, Kobe, Japan. sugita@vision-care.jp.; Vision Care Inc, Kobe, Japan. sugita@vision-care.jp.
Jazyk: angličtina
Zdroj: Communications medicine [Commun Med (Lond)] 2024 Sep 30; Vol. 4 (1), pp. 187. Date of Electronic Publication: 2024 Sep 30.
DOI: 10.1038/s43856-024-00617-5
Abstrakt: 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.
(© 2024. The Author(s).)
Databáze: MEDLINE
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