Müller glia fused with adult stem cells undergo neural differentiation in human retinal models

Bonilla-Pons, Sergi A.; 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; Cosma, María Pía

doi:10.1016/j.ebiom.2022.103914

Cited by 7 publications

(5 citation statements)

References 86 publications

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“…The epigenetic plasticity of Müller glia in zebrafish enables the glia to undergo a reprogramming process in response to injury and produce RPCs, which later differentiate into all types of retinal cells to repair the damaged retina and restore vision. However, because of the limited epigenetic plasticity, the reprogramming ability of mammalian Müller glial cells is weak ( Bonilla-Pons et al, 2022 ). Epigenetic regulation of reprogramming in mammalian Müller glial cells produced a small number of retinal neurons, bipolar cells, and rod photoreceptors in late stage of growth ( VandenBosch et al, 2020 ; Sanhueza Salas et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

“…In zebrafish and other lower vertebrate models, retinal Müller glial cells dedifferentiated into retinal precursor cells and further differentiated into mature photoreceptors, ganglion cells, and interneurons ( Thummel et al, 2008 ; Lenkowski et al, 2013 ). However, compared with lower vertebrates, the differentiation probability of mammalian Müller glial cells under degenerative or injured conditions is very low, which does not meet the requirements for retinal self-healing ( Ahmad et al, 2020 ; Bonilla-Pons et al, 2022 ). Recently, based on the understanding of the reprogramming mechanism of Müller glial cells in zebrafish, appropriate tools and methods have been established to improve the induction of Müller glial reprogramming in mammals.…”

Section: Introductionmentioning

confidence: 99%

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Epigenetic mechanisms of Müller glial reprogramming mediating retinal regeneration

Zhang

et al. 2023

Front. Cell Dev. Biol.

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Retinal degenerative diseases, characterized by retinal neuronal death and severe vision loss, affect millions of people worldwide. One of the most promising treatment methods for retinal degenerative diseases is to reprogram non-neuronal cells into stem or progenitor cells, which then have the potential to re-differentiate to replace the dead neurons, thereby promoting retinal regeneration. Müller glia are the major glial cell type and play an important regulatory role in retinal metabolism and retinal cell regeneration. Müller glia can serve as a source of neurogenic progenitor cells in organisms with the ability to regenerate the nervous system. Current evidence points toward the reprogramming process of Müller glia, involving changes in the expression of pluripotent factors and other key signaling molecules that may be regulated by epigenetic mechanisms. This review summarizes recent knowledge of epigenetic modifications involved in the reprogramming process of Müller glia and the subsequent changes to gene expression and the outcomes. In living organisms, epigenetic mechanisms mainly include DNA methylation, histone modification, and microRNA–mediated miRNA degradation, all of which play a crucial role in the reprogramming process of Müller glia. The information presented in this review will improve the understanding of the mechanisms underlying the Müller glial reprogramming process and provide a research basis for the development of Müller glial reprogramming therapy for retinal degenerative diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Epigenetic mechanisms of Müller glial reprogramming mediating retinal regeneration

Zhang

et al. 2023

Front. Cell Dev. Biol.

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“…Cells were cultivated at 5 × 10 4 cells/cm 2 for one day in a cell culture flask (Corning). 71 Müller-rot and Müller cells were used as controls without cocultivation.…”

Section: Methodsmentioning

confidence: 99%

Mitochondrial transfer between BMSCs and Müller promotes mitochondrial fusion and suppresses gliosis in degenerative retina

Huang,

Luodan A,

Gao

et al. 2024

iScience

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“…An unusual study by Bonilla-Pons et al [ 289 ] has been conducted on an organotypic culture of NR using cell fusion technology. As a result, it turns out that, as in mice [ 290 ], human MGCs can fuse with human mesenchymal stem cells, giving rise to hybrid cells.…”

Section: Intrinsic Retinal Regeneration Cell Sources and Their Implic...mentioning

confidence: 99%

“…Such hybrids are capable of producing retinal neurons, and their pretreatment with the activator Wnt/β-catenin increases their differentiation into neuronal-like cells, providing the ability of the hybrid descendants to migrate, engraft, and manifest neural, proto-electrophysiological properties. The authors [ 289 ] suggest that this technique of cell fusion-mediated MGC reprogramming and neurogenesis in the human NR is another potential therapeutic approach to cell regeneration for the treatment of human NR diseases. It should also be mentioned that the presence of stem cells is known to enrich the cell environment in trophic molecules and self-renewal factors and to enhance cell homing and survival [ 291 , 292 ].…”

Section: Intrinsic Retinal Regeneration Cell Sources and Their Implic...mentioning

confidence: 99%

Cell Sources for Retinal Regeneration: Implication for Data Translation in Biomedicine of the Eye

Grigoryan

2022

Cells

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The main degenerative diseases of the retina include macular degeneration, proliferative vitreoretinopathy, retinitis pigmentosa, and glaucoma. Novel approaches for treating retinal diseases are based on cell replacement therapy using a variety of exogenous stem cells. An alternative and complementary approach is the potential use of retinal regeneration cell sources (RRCSs) containing retinal pigment epithelium, ciliary body, Müller glia, and retinal ciliary region. RRCSs in lower vertebrates in vivo and in mammals mostly in vitro are able to proliferate and exhibit gene expression and epigenetic characteristics typical for neural/retinal cell progenitors. Here, we review research on the factors controlling the RRCSs’ properties, such as the cell microenvironment, growth factors, cytokines, hormones, etc., that determine the regenerative responses and alterations underlying the RRCS-associated pathologies. We also discuss how the current data on molecular features and regulatory mechanisms of RRCSs could be translated in retinal biomedicine with a special focus on (1) attempts to obtain retinal neurons de novo both in vivo and in vitro to replace damaged retinal cells; and (2) investigations of the key molecular networks stimulating regenerative responses and preventing RRCS-related pathologies.

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Müller glia fused with adult stem cells undergo neural differentiation in human retinal models

Cited by 7 publications

References 86 publications

Epigenetic mechanisms of Müller glial reprogramming mediating retinal regeneration

Epigenetic mechanisms of Müller glial reprogramming mediating retinal regeneration

Mitochondrial transfer between BMSCs and Müller promotes mitochondrial fusion and suppresses gliosis in degenerative retina

Cell Sources for Retinal Regeneration: Implication for Data Translation in Biomedicine of the Eye

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