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

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...

Full description

Saved in:
Bibliographic Details
Published inScience translational medicine Vol. 11; no. 475
Main Authors Sharma, Ruchi, Khristov, Vladimir, Rising, Aaron, Jha, Balendu Shekhar, Dejene, Roba, Hotaling, Nathan, Li, Yichao, Stoddard, Jonathan, Stankewicz, Casey, Wan, Qin, Zhang, Connie, Campos, Mercedes Maria, Miyagishima, Kiyoharu J, McGaughey, David, Villasmil, Rafael, Mattapallil, Mary, Stanzel, Boris, Qian, Haohua, Wong, Wai, Chase, Lucas, Charles, Steve, McGill, Trevor, Miller, Sheldon, Maminishkis, Arvydas, Amaral, Juan, Bharti, Kapil
Format Journal Article
LanguageEnglish
Published United States 16.01.2019
Subjects
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
Online AccessGet more information

Cover

More Information
Summary: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.
ISSN:1946-6242
DOI:10.1126/scitranslmed.aat5580