Hybrid Müller Glia and Adult Stem Cells "Awaken" Potential for Mammalian Retinal Regeneration

Article: Cell fusion ‘awakens’ regenerative potential of human retina
Source: Centre for Genomic Regulation (Spain)
Published: March 15, 2022

Immunostaining of human retinal organoids microinjected with hybrids.
Cell fusion is enhanced by activation of the Wnt/beta-catenin pathway (top).  

Müller glia are support cells in the retina where they perform a variety of functions, from channeling light to mitigating cellular stress. The Müller glia of lower vertebrates, such as salamanders and fish, have the capacity to regenerate neural tissue—that is, engage in mitosis—in response to retinal damage; however, this capacity is lost in mammalian retinas and visual impairment due to retinal damage is permanent. Researchers in Spain wanted to explore the regenerative potential of these glial cells combined with stem cells as a therapeutic opportunity in humans, noting that cell fusion events, although rare, also occur in human tissues of the liver, brain, and gastrointestinal tract. In the study, the team of scientists conducted in vitro fusion of Müller glia and cells derived from adult human mesenchymal and hematopoietic stem and progenitor cells (adipose and bone marrow stem cells). The resulting hybrid cells were then injected into a retinal organoid model, where they were observed to successfully engraft into the tissue and differentiate into cells that closely resemble retinal ganglion cells. The authors write, importantly, "cell fusion efficiency is enhanced by inflammatory signals [from the retina] and that the activation of the Wnt/beta-catenin pathway increases differentiation of the hybrids into neuronal-like cells." The findings show that Müller glia retain regenerative activity, and that hybrids between Müller glia and adult stem cells might be a promising stem cell-mediated therapy for human retina regeneration that could be used to treat visual impairment. The researchers next plan to investigate why the hybrid cells, with four complete sets of chromosomes, do not result in chromosomal instability or cancer development; they hypothesize that cells of the retina have a mechanism that acts as a genetic reservoir (similar to those found in the human liver) to regulate chromosome segregation. 

My rating of this study: ⭐⭐

Bonilla-Pons SA, Nakagawa S, Bahima EG, et al. "Müller glia fused with adult stem cells undergo neural differentiation in human retinal models." eBioMedicine.  77:103914. 1 March 2022. https://doi.org/10.1016/j.ebiom.2022.103914