Development of a Manufacturing Process for Clinical Autologous hiPSC-Derived Retinal Pigment Epithelium.

Age-related macular degeneration (AMD) is a leading cause of irreversible vision loss. The disease progresses through early, intermediate, and advanced stages, with late forms including dry AMD (geographic atrophy) and wet AMD (choroidal neovascularization). Currently, there is no cure for dry AMD, which results from retinal pigment epithelium (RPE) cell loss. Induced pluripotent stem cell (iPSC)-based transplants offer a potential therapy by replacing atrophied RPE. This chapter outlines the manufacturing process, key parameters, and challenges of developing iPSC-derived RPE therapy. We engineered a clinical-grade iPSC-RPE patch using autologous cells from AMD patients. Starting from the patient blood, CD34+ cells were isolated, expanded, and reprogrammed using episomal plasmids. Twelve iPSC clones were generated, quality-tested, and three were selected for differentiation into mature RPE on a biodegradable scaffold. The final patch underwent QC assays for donor identity, sterility, and phenotype confirmation before transplantation. This work has led to a Phase I/IIa clinical trial to evaluate the safety and feasibility of auto-iPSC-RPE patches in AMD patients.