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

Ruchi Sharma, Vladimir Khristov, Aaron Rising, Balendu Shekhar Jha, Roba Dejene, Nathan Hotaling, Yichao Li, Jonathan Stoddard, Casey Stankewicz, Qin Wan, Connie Zhang, Mercedes Maria Campos, Kiyoharu J. Miyagishima, David McGaughey, Rafael Villasmil, Mary Mattapallil, Boris Stanzel, Haohua Qian, Wai Wong, Lucas Chase & 6 others Steve Charles, Trevor McGill, Sheldon Miller, Arvydas Maminishkis, Juan Amaral, Kapil Bharti

Research output: Contribution to journalArticle

2 Citations (Scopus)

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.

Original languageEnglish (US)
Article numbereaat5580
JournalScience Translational Medicine
Volume11
Issue number475
DOIs
StatePublished - Jan 16 2019

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Retinal Degeneration
Retinal Pigment Epithelium
Induced Pluripotent Stem Cells
Rodentia
Swine
Stem Cells
Macular Degeneration
Mutation
Cell- and Tissue-Based Therapy
Suspensions
Lasers
Transplantation
Wounds and Injuries

ASJC Scopus subject areas

  • Medicine(all)

Cite this

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

In: Science Translational Medicine, Vol. 11, No. 475, eaat5580, 16.01.2019.

Research output: Contribution to journalArticle

Sharma, R, Khristov, V, Rising, A, Jha, BS, Dejene, R, Hotaling, N, Li, Y, Stoddard, J, Stankewicz, C, Wan, Q, Zhang, C, Campos, MM, Miyagishima, KJ, McGaughey, D, Villasmil, R, Mattapallil, M, Stanzel, B, Qian, H, Wong, W, Chase, L, Charles, S, McGill, T, Miller, S, Maminishkis, A, Amaral, J & Bharti, K 2019, 'Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs' Science Translational Medicine, vol. 11, no. 475, eaat5580. https://doi.org/10.1126/scitranslmed.aat5580
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. / Clinical-grade stem cell-derived retinal pigment epithelium patch rescues retinal degeneration in rodents and pigs. In: Science Translational Medicine. 2019 ; Vol. 11, No. 475.
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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.",
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AU - Hotaling, Nathan

AU - Li, Yichao

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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

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