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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.

Author information

1
Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA.
2
Section on Epithelial and Retinal Physiology and Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
3
Visual Function Core, National Eye Institute, NIH, Bethesda, MD 20892, USA.
4
Casey Eye Institute, Oregon Health & Science University, Portland, OR 97239, USA.
5
Cellular Dynamics International Inc. (a FUJIFILM company), Madison, WI 53711, USA.
6
Histology Core, National Eye Institute, NIH, Bethesda, MD 20892, USA.
7
Ophthalmic Genetics and Visual Functional Branch, National Eye Institute, NIH, Bethesda, MD 20892, USA.
8
Flow Cytometry Core, National Eye Institute, NIH, Bethesda, MD 20892, USA.
9
Laboratory of Immunology, National Eye Institute, NIH, Bethesda, MD 20892, USA.
10
Macula Center Saar, Sulzbach Knappschaft Eye Clinic, Sulzbach/Saar 66280, Germany.
11
Unit on Neuron-Glia Interactions in Retinal Disease, National Eye Institute, NIH, Bethesda, MD 20892, USA.
12
Charles Retina Institute, Germantown, TN 38138, USA.
13
Office of Scientific Director, National Eye Institute, NIH, Bethesda, MD 20892, USA.
14
Unit on Ocular and Stem Cell Translational Research, National Eye Institute, NIH, Bethesda, MD 20892, USA. Kapilbharti@nei.nih.gov.

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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