Characterization and Transplantation of CD73-Positive Photoreceptors Isolated from Human iPSC-Derived Retinal Organoids

Summary: Photoreceptor degenerative diseases are a major cause of blindness for which cell replacement is one of the most encouraging strategies. For stem cell-based therapy using human induced pluripotent stem cells (hiPSCs), it is crucial to obtain a homogenous photoreceptor cell population. We co...

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Main Authors: Giuliana Gagliardi, Karim Ben M'Barek, Antoine Chaffiol, Amélie Slembrouck-Brec, Jean-Baptiste Conart, Céline Nanteau, Oriane Rabesandratana, José-Alain Sahel, Jens Duebel, Gael Orieux, Sacha Reichman, Olivier Goureau
Format: Article
Language:English
Published: Elsevier 2018-09-01
Series:Stem Cell Reports
Online Access:http://www.sciencedirect.com/science/article/pii/S2213671118303102
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Summary:Summary: Photoreceptor degenerative diseases are a major cause of blindness for which cell replacement is one of the most encouraging strategies. For stem cell-based therapy using human induced pluripotent stem cells (hiPSCs), it is crucial to obtain a homogenous photoreceptor cell population. We confirmed that the cell surface antigen CD73 is exclusively expressed in hiPSC-derived photoreceptors by generating a fluorescent cone rod homeobox (Crx) reporter hiPSC line using CRISPR/Cas9 genome editing. We demonstrated that CD73 targeting by magnetic-activated cell sorting (MACS) is an effective strategy to separate a safe population of transplantable photoreceptors. CD73+ photoreceptor precursors can be isolated in large numbers and transplanted into rat eyes, showing capacity to survive and mature in close proximity to host inner retina of a model of photoreceptor degeneration. These data demonstrate that CD73+ photoreceptor precursors hold great promise for a future safe clinical translation. : Gagliardi and colleagues show the possibility of isolating a homogeneous and functional population of photoreceptors from human induced pluripotent stem cells by targeting of a single surface antigen, CD73. Transplanted human cells are able to be incorporated into a host retina, generating mostly cone photoreceptors. Keywords: retina, photoreceptor, organoids, cell sorting, neurodegeneration, transplantation, iPSC, cell therapy
ISSN:2213-6711