Abstract
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.
Highlights
Immunosuppressive medications are used for patients with ocular inflammation in Japan
Similar to the results seen after allogeneic RPE cell transplantation in monkeys [20,21], we found fluorescein angiography (FA) leakages from the transplanted human iPSC-RPE cells, but no abnormal sign around the transplanted area by optical coherence tomography (OCT) in the HM-1 monkey (Figure S2) was observed
We evaluated the best concentration of each drug for the in vitro assay
Summary
Immunosuppressive medications are used for patients with ocular inflammation in Japan. Patients with uveitis and other ocular inflammatory diseases receive betamethasone and dexamethasone (eye drops), triamcinolone (injection) [1], and prednisolone (oral). Immunosuppressants, including biologics such as cyclosporine A and FK506 (oral) [2], infliximab (intravenous) [3], and adalimumab (subcutaneous injection) [4], are used. We have proper protocols for the treatment of ocular inflammation diseases, at the moment, we have no answer nor evidence about the treatment of immune rejections after retinal cell transplantation. The final goal of our study is to establish a new regenerative therapy with iPSC-RPE cells that can be used worldwide, which includes the postoperative medication
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