A Chemical Reprogramming Approach Efficiently Producing Human Retinal Pigment Epithelium Cells for Retinal Disease Therapies.

Abstract

Human induced pluripotent stem cells (hiPSCs) represent a promising cell source for generating functional cells suitable for clinical therapeutic applications, particularly in the context of autologous cell therapies. However, the production of hiPSCs through genetic manipulation, especially involving oncogenes, may raise safety concerns. Furthermore, the complexity and high costs associated with hiPSCs generation have hindered their broad clinical use. In this study, we utilised a recently developed chemical reprogramming method in conjunction with a guided differentiation protocol, introducing a chemically defined strategy for generating functional human retinal pigment epithelium (RPE) cells from adipose tissue, bypassing conventional hiPSCs generation challenges. By utilising small molecule-based chemical cocktails, we reprogrammed somatic adipose cells into human chemically induced pluripotent stem cells (hCiPSCs) in a safer and more streamlined manner, entirely free from gene manipulation. Subsequent differentiation of hCiPSCs into functional RPE cells demonstrated their capability for secretion and phagocytosis, emphasising their vital role in maintaining retinal homeostasis and underscoring their therapeutic potential. Our findings highlight the transformative potential of hCiPSCs as a safer, more efficient option for personalised cell therapies, with applications extending beyond ocular disease to a wide range of medical conditions.