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Article

A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models

1
Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan
2
Department of Ophthalmology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0114, Japan
3
Department of Ophthalmology & Visual Science, Tokyo Medical and Dental University Graduate School of Medical and Dental Sciences, 1-5-45, Yushima, Bunkyo-Ku, Tokyo 113-8510, Japan
4
Department of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, Japan
5
Department of Ophthalmology, Kobe City Eye Hospital, 2-1-8 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Int. J. Mol. Sci. 2020, 21(9), 3077; https://doi.org/10.3390/ijms21093077
Received: 13 April 2020 / Revised: 25 April 2020 / Accepted: 26 April 2020 / Published: 27 April 2020
Recently, we successfully transplanted an autograft, or major histocompatibility complex (MHC)-matched allografts, from induced-pluripotent-stem-cell-derived retinal pigment epithelial (iPSC-RPE) cells in patients with age-related macular degeneration. However, there was an issue regarding immune rejection after transplantation. In this study, we established a preoperational in vitro “drug–lymphocytes–grafts immune reaction (Drug-LGIR)” test to determine the medication for immune rejection using host immunocompetent cells (lymphocytes) and transplant cells (target iPSC-RPE cells) together with different medications. The adequacy of the test was assessed by in vivo transplantation in monkey models together with medication based on in vitro data. In the results of Drug-LGIR tests, some drugs exhibited significant suppression of RPE cell-related allogeneic reactions, while other drugs did not, and the efficacy of each drug differed among the recipient monkeys. Based on the results of Drug-LGIR, we applied cyclosporine A or local steroid (triamcinolone) therapy to two monkeys, and successfully suppressed RPE-related immune rejections with RPE grafts, which survived without any signs of rejection under drug administration. We propose that our new preoperational in vitro Drug-LGIR test, which specifies the most efficacious medication for each recipient, is useful for controlling immune attacks with personalized treatment for each patient after retinal transplantation. View Full-Text
Keywords: iPS cells; retinal pigment epithelial cells; immune rejection; drug; transplantation iPS cells; retinal pigment epithelial cells; immune rejection; drug; transplantation
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MDPI and ACS Style

Fujii, S.; Sugita, S.; Futatsugi, Y.; Ishida, M.; Edo, A.; Makabe, K.; Kamao, H.; Iwasaki, Y.; Sakaguchi, H.; Hirami, Y.; Kurimoto, Y.; Takahashi, M. A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models. Int. J. Mol. Sci. 2020, 21, 3077. https://doi.org/10.3390/ijms21093077

AMA Style

Fujii S, Sugita S, Futatsugi Y, Ishida M, Edo A, Makabe K, Kamao H, Iwasaki Y, Sakaguchi H, Hirami Y, Kurimoto Y, Takahashi M. A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models. International Journal of Molecular Sciences. 2020; 21(9):3077. https://doi.org/10.3390/ijms21093077

Chicago/Turabian Style

Fujii, Shota, Sunao Sugita, Yoko Futatsugi, Masaaki Ishida, Ayaka Edo, Kenichi Makabe, Hiroyuki Kamao, Yuko Iwasaki, Hirokazu Sakaguchi, Yasuhiko Hirami, Yasuo Kurimoto, and Masayo Takahashi. 2020. "A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models" International Journal of Molecular Sciences 21, no. 9: 3077. https://doi.org/10.3390/ijms21093077

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