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Title: Müller glia fused with adult stem cells undergo neural differentiation in human retinal models
Author: Bonilla Pons, Sergi Àngel
Nakagawa, Shoma
Garreta, Elena
Fernández Blanco, Álvaro
Pesaresi, Martina
Antin, Justin Christopher d'
Sebastian Perez, Ruben
Greco, Daniela
Domínguez Sala, Eduardo
Gómez Riera, Raúl
Barraquer Compte, Rafael Igancio
Dierssen, Mara
Montserrat Pulido, Núria
Cosma, Maria Pia
Keywords: Trastorns de la visió
Medicina regenerativa
Vision disorders
Regenerative medicine
Issue Date: 9-Mar-2022
Publisher: Elsevier
Abstract: Visual impairments are a critical medical hurdle to be addressed in modern society. Müller glia (MG) have regenerative potential in the retina in lower vertebrates, but not in mammals. However, in mice, in vivo cell fusion between MG and adult stem cells forms hybrids that can partially regenerate ablated neurons.We used organotypic cultures of human retina and preparations of dissociated cells to test the hypothesis that cell fusion between human MG and adult stem cells can induce neuronal regeneration in human systems. Moreover, we established a microinjection system for transplanting human retinal organoids to demonstrate hybrid differentiation.We first found that cell fusion occurs between MG and adult stem cells, in organotypic cultures of human retina as well as in cell cultures. Next, we showed that the resulting hybrids can differentiate and acquire a proto-neural electrophysiology profile when the Wnt/beta-catenin pathway is activated in the adult stem cells prior fusion. Finally, we demonstrated the engraftment and differentiation of these hybrids into human retinal organoids.We show fusion between human MG and adult stem cells, and demonstrate that the resulting hybrid cells can differentiate towards neural fate in human model systems. Our results suggest that cell fusion-mediated therapy is a potential regenerative approach for treating human retinal dystrophies.This work was supported by La Caixa Health (HR17-00231), Velux Stiftung (976a) and the Ministerio de Ciencia e Innovación, (BFU2017-86760-P) (AEI/FEDER, UE), AGAUR (2017 SGR 689, 2017 SGR 926).Published by Elsevier B.V.
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It is part of: Ebiomedicine, 2022, vol. 77
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ISSN: 2352-3964
Appears in Collections:Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC))

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