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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Disease Models, Animal
  • Macular Degeneration / pathology
  • Macular Degeneration / therapy
  • Rats
  • Retinal Degeneration / pathology
  • Retinal Degeneration / therapy*
  • Retinal Pigment Epithelium / cytology*
  • Stem Cells / cytology*
  • Swine