Journal
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
Volume 21, Issue 9, Pages -Publisher
MDPI
DOI: 10.3390/ijms21093077
Keywords
iPS cells; retinal pigment epithelial cells; immune rejection; drug; transplantation
Funding
- Research Center Network for Realization of Regenerative Medicine from the Japan Agency for Medical Research and Development (AMED)
- Ministry of Education, Culture, Sports, Science and Technology of Japan [18H02959]
- RIKEN Junior Research Associate Program
- Grants-in-Aid for Scientific Research [18H02959] Funding Source: KAKEN
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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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