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Müller glia fused with adult stem cells undergo neural differentiation in human retinal models
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...
Autores principales: | , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Elsevier
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917309/ https://www.ncbi.nlm.nih.gov/pubmed/35278743 http://dx.doi.org/10.1016/j.ebiom.2022.103914 |
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author | Bonilla-Pons, Sergi Àngel Nakagawa, Shoma Bahima, Elena Garreta Fernández-Blanco, Álvaro Pesaresi, Martina D'Antin, Justin Christopher Sebastian-Perez, Ruben Greco, Daniela Domínguez-Sala, Eduardo Gómez-Riera, Raúl Compte, Rafael Ignacio Barraquer Dierssen, Mara Pulido, Nuria Montserrat Cosma, Maria Pia |
author_facet | Bonilla-Pons, Sergi Àngel Nakagawa, Shoma Bahima, Elena Garreta Fernández-Blanco, Álvaro Pesaresi, Martina D'Antin, Justin Christopher Sebastian-Perez, Ruben Greco, Daniela Domínguez-Sala, Eduardo Gómez-Riera, Raúl Compte, Rafael Ignacio Barraquer Dierssen, Mara Pulido, Nuria Montserrat Cosma, Maria Pia |
author_sort | Bonilla-Pons, Sergi Àngel |
collection | PubMed |
description | 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. 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). |
format | Online Article Text |
id | pubmed-8917309 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Elsevier |
record_format | MEDLINE/PubMed |
spelling | pubmed-89173092022-03-13 Müller glia fused with adult stem cells undergo neural differentiation in human retinal models Bonilla-Pons, Sergi Àngel Nakagawa, Shoma Bahima, Elena Garreta Fernández-Blanco, Álvaro Pesaresi, Martina D'Antin, Justin Christopher Sebastian-Perez, Ruben Greco, Daniela Domínguez-Sala, Eduardo Gómez-Riera, Raúl Compte, Rafael Ignacio Barraquer Dierssen, Mara Pulido, Nuria Montserrat Cosma, Maria Pia EBioMedicine Articles 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. 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). Elsevier 2022-03-09 /pmc/articles/PMC8917309/ /pubmed/35278743 http://dx.doi.org/10.1016/j.ebiom.2022.103914 Text en https://creativecommons.org/licenses/by-nc-nd/4.0/This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/). |
spellingShingle | Articles Bonilla-Pons, Sergi Àngel Nakagawa, Shoma Bahima, Elena Garreta Fernández-Blanco, Álvaro Pesaresi, Martina D'Antin, Justin Christopher Sebastian-Perez, Ruben Greco, Daniela Domínguez-Sala, Eduardo Gómez-Riera, Raúl Compte, Rafael Ignacio Barraquer Dierssen, Mara Pulido, Nuria Montserrat Cosma, Maria Pia Müller glia fused with adult stem cells undergo neural differentiation in human retinal models |
title | Müller glia fused with adult stem cells undergo neural differentiation in human retinal models |
title_full | Müller glia fused with adult stem cells undergo neural differentiation in human retinal models |
title_fullStr | Müller glia fused with adult stem cells undergo neural differentiation in human retinal models |
title_full_unstemmed | Müller glia fused with adult stem cells undergo neural differentiation in human retinal models |
title_short | Müller glia fused with adult stem cells undergo neural differentiation in human retinal models |
title_sort | müller glia fused with adult stem cells undergo neural differentiation in human retinal models |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8917309/ https://www.ncbi.nlm.nih.gov/pubmed/35278743 http://dx.doi.org/10.1016/j.ebiom.2022.103914 |
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