Clinical‐grade hPSC‐derived RPE grafts for the treatment of age‐related macular degeneration

Abstract

Aims/Purpose: Age‐related Macular Degeneration (AMD), a prevalent global cause of vision loss in the elderly, necessitates the development of efficacious treatments. Existing therapies do not cure AMD due to its complexity and the irreversible loss of photoreceptors and Retinal Pigment Epithelium (RPE). Cell replacement therapies targeting faulty RPE cells offer potential for slowing AMD progression, but the immunocompatibility of such therapies is challenging. We aim to develop a cell therapy strategy to minimize immune rejection.Methods: Our strategy entailed establishing a Good Manufacturing Practice (GMP)‐compatible induced Pluripotent Stem Cell (iPSC) cell bank representing the most frequent homozygous human leukocyte antigen (HLA) haplotypes in the Andalusian population, facilitating derivation of immunocompatible RPE cells. We utilized and refined existing RPE differentiation protocols for generating clinically compliant RPE cells. Furthermore, we tested three bioscaffolds for RPE growth and maturation and compared the physical properties of the resulting RPE cell‐bioscaffold biopatch for transplantability.Results: We successfully established three GMP‐compatible iPSC lines featuring common homozygous HLA profiles. Through our refined differentiation protocols, these iPSCs were converted into functional, high‐purity and safe RPE cells. Comparative analysis of different bioscaffolds revealed variable capabilities for RPE growth, maturation and transplantability, thereby informing the final bioscaffold selection for RPE biopatch generation.Conclusions: Our study underscores the feasibility of generating clinical‐grade, immunocompatible iPSC‐derived RPE grafts using GMP‐compliant procedures for AMD treatment. This innovative approach addresses a critical unmet medical need and suggests potential for similar strategies in other cell replacement therapies. The selection of an optimal bioscaffold for RPE growth and maturation is critical for effective RPE biopatch development. Further pre‐clinical and clinical studies are required to evaluate the safety and efficacy of these RPE grafts in AMD treatment.