Müller glia fused with adult stem cells undergo neural differentiation in human retinal models
Author
Bonilla-Pons, Sergi Àngel
Nakagawa, Shoma
Garreta Bahima, Elena
Fernández-Blanco, Álvaro
Pesaresi, Martina
D'Antin, Justin Christopher
Perez, Ruben Sebastian
Greco, Daniela
Domínguez-Sala, Eduardo
Gómez-Riera, Raúl
Barraquer Compte, Rafael Ignacio
Dierssen, Mara
Pulido, Nuria Montserrat
Cosma, Maria Pia
Publication date
2022ISSN
2352-3964
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.
Document Type
Article
Document version
Published version
Language
English
Subject (CDU)
617 - Surgery. Orthopaedics. Ophthalmology
Keywords
Regeneració de la retina
Fusió cel·lular
Organoides
Cèl·lula mare
Diferenciació neuronal
Muller glia
Regeneración de retina
Fusión celular
Organoides
Célula madre
Diferenciación neuronal
Müller glía
Retina regeneration
Cell fusion
Organoids
Stem cell
Neural differentiation
Muller glia
Pages
22
Publisher
Elsevier
Collection
77
Is part of
eBioMedicine
Citation
Bonilla-Pons, Sergi Àngel; Nakagawa, Shoma; Garreta Bahima, Elena [et al.]. Müller glia fused with adult stem cells undergo neural differentiation in human retinal models. eBioMedicine, 2022, 77, 103914. Disponible en: <https://www.sciencedirect.com/science/article/pii/S2352396422000986?via%3Dihub>. Fecha de acceso: 14 feb. 2024. DOI: 10.1016/j.ebiom.2022.103914.
This item appears in the following Collection(s)
- Ciències de la Salut [725]
Rights
© Under a Creative Commons license.
Except where otherwise noted, this item's license is described as https://creativecommons.org/licenses/by-nc-nd/4.0/