Sci Transl Med. 2019 Jan 16;11(475). pii: eaat5580. doi: 10.1126/scitranslmed.aat5580.

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

Sharma R¹, Khristov V², Rising A², Jha BS¹, Dejene R¹, Hotaling N¹, Li Y³, Stoddard J⁴, Stankewicz C⁵, Wan Q², Zhang C², Campos MM⁶, Miyagishima KJ², McGaughey D⁷, Villasmil R⁸, Mattapallil M⁹, Stanzel B¹⁰, Qian H³, Wong W¹¹, Chase L⁵, Charles S¹², McGill T⁴, Miller S², Maminishkis A², Amaral J¹³, Bharti K¹⁴.

Abstract

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.