Müller glia fused with adult stem cells undergo neural differentiation in human retinal models
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- dc.contributor.author Bonilla-Pons, Sergi A.
- dc.contributor.author Nakagawa, Shoma
- dc.contributor.author Garreta Bahima, Elena
- dc.contributor.author Fernández-Blanco, Álvaro
- dc.contributor.author Pesaresi, Martina, 1991-
- dc.contributor.author D'Antin, Justin Christopher
- dc.contributor.author Sebastián Pérez, Rubén
- dc.contributor.author Greco, Daniela
- dc.contributor.author Domínguez-Sala, Eduardo
- dc.contributor.author Gómez-Riera, Raúl
- dc.contributor.author Barraquer Compte, Rafael Ignacio
- dc.contributor.author Dierssen, Mara
- dc.contributor.author Montserrat Pulido, Núria
- dc.contributor.author Cosma, Maria Pia
- dc.date.accessioned 2022-04-05T10:07:31Z
- dc.date.available 2022-04-05T10:07:31Z
- dc.date.issued 2022
- dc.description.abstract Background: 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. Methods: 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. Findings: 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. Interpretation: 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.
- dc.description.sponsorship Funding: 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)
- dc.format.mimetype application/pdf
- dc.identifier.citation Bonilla-Pons SA, Nakagawa S, Garreta Bahima E, Férnandez-Blanco A, Pesaresi M, D'Antin JC. Müller glia fused with adult stem cells undergo neural differentiation in human retinal models. EBioMedicine. 2022 Mar;77:103914. DOI: 10.1016/j.ebiom.2022.103914
- dc.identifier.doi http://dx.doi.org/10.1016/j.ebiom.2022.103914
- dc.identifier.issn 2352-3964
- dc.identifier.uri http://hdl.handle.net/10230/52829
- dc.language.iso eng
- dc.publisher Elsevier
- dc.relation.projectID info:eu-repo/grantAgreement/ES/2PE/BFU2017-86760-P
- dc.rights This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/)
- dc.rights.accessRights info:eu-repo/semantics/openAccess
- dc.rights.uri https://creativecommons.org/licenses/by-nc-nd/4.0/
- dc.subject.other Retina -- Malalties
- dc.subject.other Genètica
- dc.title Müller glia fused with adult stem cells undergo neural differentiation in human retinal models
- dc.type info:eu-repo/semantics/article
- dc.type.version info:eu-repo/semantics/publishedVersion