Generation of universal retinal pigment epithelium derived from human induced pluripotent stem cells for treatment of age-related macular degeneration (AMD) patients

We will develop universal human induced pluripotent stem cells (hiPSCs) without gene editing, which do not show human leukocyte antigen (HLA) class I and class II where universal hiPSCs and their differentiated cells do not show immune rejection when these cells are transplanted into any patients having different HLA class I and class II types. Our innovative universal hiPSCs are prepared by mixing amniotic fluids obtained from multi donors where no immune rejection of the stem cells (universal amniotic fluid stem cells) can be survived during the mixing of allogenic amniotic fluids from multi donors (Key technology of this project, under submission into US patent, A. Higuchi et al., Cell Prolif, 54 (2021) e12995)), whereas conventional universal hiPSCs are prepared using gene editing such as Crispr/Cas9 technology, which are difficult to be approved in clinical application because of their gene editing. Universal hiPSCs are differentiated into retinal pigment epithelium (RPE) using several inhibitors to speed up their differentiation. We will develop optimal differentiation protocol and optimal cell culture materials for differentiation of universal hiPSCs into RPE with high efficiency and high purity. Universal hiPSC-derived RPE will be characterized and transplanted into Royal College of Surgeons (RCS) rats subretinally, which are an animal model of dry AMD disease. We will compare pigmentation (RPE survival) on rats’ eyes, where conventional hESC(H9)-derived RPE and universal hiPSC-derived RPE are transplanted subretinally. We will evaluate advantages of usage of universal hiPSC-derived RPE transplantation in the animal model of dry AMD disease for future clinical application of transplantation of universal hiPSC-derived RPE into patients with dry AMD and Stargardt’s macular dystrophy. Our final goal of this project is to develop off-the-shelf universal hiPSC-derived RPE for treatment of any patients with dry AMD and Stargardt’s macular dystrophy without usage of immunosuppressive medicine.