TY - JOUR
T1 - Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs
AU - Sharma, Ruchi
AU - Khristov, Vladimir
AU - Rising, Aaron
AU - Jha, Balendu Shekhar
AU - Dejene, Roba
AU - Hotaling, Nathan
AU - Li, Yichao
AU - Stoddard, Jonathan
AU - Stankewicz, Casey
AU - Wan, Qin
AU - Zhang, Connie
AU - Campos, Mercedes Maria
AU - Miyagishima, Kiyoharu J.
AU - McGaughey, David
AU - Villasmil, Rafael
AU - Mattapallil, Mary
AU - Stanzel, Boris
AU - Qian, Haohua
AU - Wong, Wai
AU - Chase, Lucas
AU - Charles, Steve
AU - McGill, Trevor
AU - Miller, Sheldon
AU - Maminishkis, Arvydas
AU - Amaral, Juan
AU - Bharti, Kapil
N1 - Publisher Copyright:
Copyright © 2019 The Authors, some rights reserved.
PY - 2019/1/16
Y1 - 2019/1/16
N2 - 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.
AB - 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.
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U2 - 10.1126/scitranslmed.aat5580
DO - 10.1126/scitranslmed.aat5580
M3 - Article
C2 - 30651323
AN - SCOPUS:85060138531
SN - 1946-6234
VL - 11
JO - Science translational medicine
JF - Science translational medicine
IS - 475
M1 - eaat5580
ER -