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

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 re...

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Autores principales: Fujii, Shota, Sugita, Sunao, Futatsugi, Yoko, Ishida, Masaaki, Edo, Ayaka, Makabe, Kenichi, Kamao, Hiroyuki, Iwasaki, Yuko, Sakaguchi, Hirokazu, Hirami, Yasuhiko, Kurimoto, Yasuo, Takahashi, Masayo
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247695/
https://www.ncbi.nlm.nih.gov/pubmed/32349277
http://dx.doi.org/10.3390/ijms21093077
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author Fujii, Shota
Sugita, Sunao
Futatsugi, Yoko
Ishida, Masaaki
Edo, Ayaka
Makabe, Kenichi
Kamao, Hiroyuki
Iwasaki, Yuko
Sakaguchi, Hirokazu
Hirami, Yasuhiko
Kurimoto, Yasuo
Takahashi, Masayo
author_facet Fujii, Shota
Sugita, Sunao
Futatsugi, Yoko
Ishida, Masaaki
Edo, Ayaka
Makabe, Kenichi
Kamao, Hiroyuki
Iwasaki, Yuko
Sakaguchi, Hirokazu
Hirami, Yasuhiko
Kurimoto, Yasuo
Takahashi, Masayo
author_sort Fujii, Shota
collection PubMed
description 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.
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spelling pubmed-72476952020-06-10 A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models Fujii, Shota Sugita, Sunao Futatsugi, Yoko Ishida, Masaaki Edo, Ayaka Makabe, Kenichi Kamao, Hiroyuki Iwasaki, Yuko Sakaguchi, Hirokazu Hirami, Yasuhiko Kurimoto, Yasuo Takahashi, Masayo Int J Mol Sci Article 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. MDPI 2020-04-27 /pmc/articles/PMC7247695/ /pubmed/32349277 http://dx.doi.org/10.3390/ijms21093077 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fujii, Shota
Sugita, Sunao
Futatsugi, Yoko
Ishida, Masaaki
Edo, Ayaka
Makabe, Kenichi
Kamao, Hiroyuki
Iwasaki, Yuko
Sakaguchi, Hirokazu
Hirami, Yasuhiko
Kurimoto, Yasuo
Takahashi, Masayo
A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models
title A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models
title_full A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models
title_fullStr A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models
title_full_unstemmed A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models
title_short A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models
title_sort strategy for personalized treatment of ips-retinal immune rejections assessed in cynomolgus monkey models
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247695/
https://www.ncbi.nlm.nih.gov/pubmed/32349277
http://dx.doi.org/10.3390/ijms21093077
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