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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| Format: | Article |
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MDPI AG
2020-04-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/9/3077 |
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| author | Shota Fujii Sunao Sugita Yoko Futatsugi Masaaki Ishida Ayaka Edo Kenichi Makabe Hiroyuki Kamao Yuko Iwasaki Hirokazu Sakaguchi Yasuhiko Hirami Yasuo Kurimoto Masayo Takahashi |
| author_facet | Shota Fujii Sunao Sugita Yoko Futatsugi Masaaki Ishida Ayaka Edo Kenichi Makabe Hiroyuki Kamao Yuko Iwasaki Hirokazu Sakaguchi Yasuhiko Hirami Yasuo Kurimoto Masayo Takahashi |
| author_sort | Shota Fujii |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T20:12:53Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T20:12:53Z |
| publishDate | 2020-04-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-ddaa8bd5e26544de8468818511ce75e72023-11-19T22:50:19ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-04-01219307710.3390/ijms21093077A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey ModelsShota Fujii0Sunao Sugita1Yoko Futatsugi2Masaaki Ishida3Ayaka Edo4Kenichi Makabe5Hiroyuki Kamao6Yuko Iwasaki7Hirokazu Sakaguchi8Yasuhiko Hirami9Yasuo Kurimoto10Masayo Takahashi11Laboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, JapanLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, JapanLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, JapanLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, JapanLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, JapanLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, JapanDepartment of Ophthalmology, Kawasaki Medical School, 577 Matsushima, Kurashiki, Okayama 701-0114, JapanDepartment 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, JapanDepartment of Ophthalmology, Osaka University Medical School, 2-2 Yamadaoka, Suita, Osaka 565-0871, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, 2-1-8 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, JapanDepartment of Ophthalmology, Kobe City Eye Hospital, 2-1-8 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, JapanLaboratory for Retinal Regeneration, RIKEN Center for Biosystems Dynamics Research, 2-2-3 Minatojima-minamimachi, Chuo-ku, Kobe 650-0047, JapanRecently, 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.https://www.mdpi.com/1422-0067/21/9/3077iPS cellsretinal pigment epithelial cellsimmune rejectiondrugtransplantation |
| spellingShingle | Shota Fujii Sunao Sugita Yoko Futatsugi Masaaki Ishida Ayaka Edo Kenichi Makabe Hiroyuki Kamao Yuko Iwasaki Hirokazu Sakaguchi Yasuhiko Hirami Yasuo Kurimoto Masayo Takahashi A Strategy for Personalized Treatment of iPS-Retinal Immune Rejections Assessed in Cynomolgus Monkey Models International Journal of Molecular Sciences iPS cells retinal pigment epithelial cells immune rejection drug transplantation |
| 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 | iPS cells retinal pigment epithelial cells immune rejection drug transplantation |
| url | https://www.mdpi.com/1422-0067/21/9/3077 |
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