Research ArticleRetinal Disease

Clinical-grade stem cell–derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs

See allHide authors and affiliations

Science Translational Medicine  16 Jan 2019:
Vol. 11, Issue 475, eaat5580
DOI: 10.1126/scitranslmed.aat5580

A pipeline for retinal stem cell therapy

Autologous induced pluripotent stem cell (iPSC)–derived retinal pigment epithelium (RPE) transplantation has been shown to improve visual function in animal models of age-related macular degeneration (AMD) and is currently being tested in human patients. However, oncogenic mutations might occur during the cell reprogramming process. Now, Sharma et al. used CD34+ peripheral blood cells from patients with AMD to generate oncogenic mutation-free iPSCs. These cells were used for the production of clinical-grade RPE cell patches. Transplantation of the RPE patches in rodent and pig models of retinal degeneration showed therapeutic effects. The authors suggest that the production process presented here might accelerate the development of safer iPSC-derived stem cell therapies.


Considerable progress has been made in testing stem cell–derived retinal pigment epithelium (RPE) as a potential therapy for age-related macular degeneration (AMD). However, the recent reports of oncogenic mutations in induced pluripotent stem cells (iPSCs) underlie the need for robust manufacturing and functional validation of clinical-grade iPSC-derived RPE before transplantation. Here, we developed oncogenic mutation-free clinical-grade iPSCs from three AMD patients and differentiated them into clinical-grade iPSC-RPE patches on biodegradable scaffolds. Functional validation of clinical-grade iPSC-RPE patches revealed specific features that distinguished transplantable from nontransplantable patches. Compared to RPE cells in suspension, our biodegradable scaffold approach improved integration and functionality of RPE patches in rats and in a porcine laser-induced RPE injury model that mimics AMD-like eye conditions. Our results suggest that the in vitro and in vivo preclinical functional validation of iPSC-RPE patches developed here might ultimately be useful for evaluation and optimization of autologous iPSC-based therapies.

View Full Text

Stay Connected to Science Translational Medicine