Molecular profiling of stem cell-derived retinal pigment epithelial cell differentiation established for clinical translation.

Autor:	Petrus-Reurer S; Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden; Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 11282 Stockholm, Sweden., Lederer AR; Laboratory of Neurodevelopmental Systems Biology, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Baqué-Vidal L; Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden., Douagi I; Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, 17177 Stockholm, Sweden., Pannagel B; Center for Hematology and Regenerative Medicine, Department of Medicine, Karolinska Institutet, 17177 Stockholm, Sweden., Khven I; Laboratory of Neurodevelopmental Systems Biology, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland., Aronsson M; Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 11282 Stockholm, Sweden., Bartuma H; Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 11282 Stockholm, Sweden., Wagner M; Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden., Wrona A; Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark., Efstathopoulos P; Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark., Jaberi E; Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark., Willenbrock H; Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark., Shimizu Y; Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark., Villaescusa JC; Cell Therapy R&D, Novo Nordisk A/S, Måløv 2760, Denmark., André H; Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 11282 Stockholm, Sweden., Sundstrӧm E; Department of Neurobiology, Care Sciences and Society, Karolinska Institutet, 17177 Stockholm, Sweden., Bhaduri A; Department of Neurology, University of California, San Francisco, CA, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA., Kriegstein A; Department of Neurology, University of California, San Francisco, CA, USA; Eli and Edythe Broad Center for Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, USA., Kvanta A; Department of Clinical Neuroscience, Division of Eye and Vision, St. Erik Eye Hospital, Karolinska Institutet, 11282 Stockholm, Sweden., La Manno G; Laboratory of Neurodevelopmental Systems Biology, Brain Mind Institute, School of Life Sciences, École Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland. Electronic address: gioele.lamanno@epfl.ch., Lanner F; Department of Clinical Sciences, Intervention and Technology, Karolinska Institutet, 17177 Stockholm, Sweden; Gynecology and Reproductive Medicine, Karolinska Universitetssjukhuset, 14186 Stockholm, Sweden; Ming Wai Lau Center for Reparative Medicine, Stockholm node, Karolinska Institutet, 17177 Stockholm, Sweden. Electronic address: fredrik.lanner@ki.se.
Jazyk:	angličtina
Zdroj:	Stem cell reports [Stem Cell Reports] 2022 Jun 14; Vol. 17 (6), pp. 1458-1475.
DOI:	10.1016/j.stemcr.2022.05.005
Abstrakt:	Human embryonic stem cell-derived retinal pigment epithelial cells (hESC-RPE) are a promising cell source to treat age-related macular degeneration (AMD). Despite several ongoing clinical studies, a detailed mapping of transient cellular states during in vitro differentiation has not been performed. Here, we conduct single-cell transcriptomic profiling of an hESC-RPE differentiation protocol that has been developed for clinical use. Differentiation progressed through a culture diversification recapitulating early embryonic development, whereby cells rapidly acquired a rostral embryo patterning signature before converging toward the RPE lineage. At intermediate steps, we identified and examined the potency of an NCAM1 + retinal progenitor population and showed the ability of the protocol to suppress non-RPE fates. We demonstrated that the method produces a pure RPE pool capable of maturing further after subretinal transplantation in a large-eyed animal model. Our evaluation of hESC-RPE differentiation supports the development of safe and efficient pluripotent stem cell-based therapies for AMD. (Copyright © 2022 The Author(s). Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
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