Cell fusion `awakens' regenerative potential of human retina
Hybrid cells could be a potential therapeutic strategy to treat retinal
damage and visual impairment

Date:
March 15, 2022
Source:
Center for Genomic Regulation
Summary:
Fusing human retinal cells with adult stem cells could be a
potential therapeutic strategy to treat retinal damage and visual
impairment, according to the findings of a new study. The hybrid
cells were injected into a growing retinal organoid, a model that
closely resembles the function of the human retina. The researchers
found that the hybrid cells successfully engrafted into the tissue
and differentiated into cells that closely resemble ganglion cells,
a type of neuron essential for vision.

The hybrid cells act by awakening the regenerative potential of
human retinal tissue, previously only thought to be the preserve
of cold-blood vertebrates.



FULL STORY ========================================================================== Fusing human retinal cells with adult stem cells could be a potential therapeutic strategy to treat retinal damage and visual impairment,
according to the findings of a new study published in the journal eBioMedicine.The hybrid cells act by awakening the regenerative potential
of human retinal tissue, previously only thought to be the preserve of cold-blood vertebrates.


==========================================================================
Cell fusion events -- the combination of two different cells into one
single entity -- are known to be a possible mechanism contributing to
tissue regeneration. Though rare in humans, the phenomenon has been consistently detected in the liver, brain, and gastrointestinal tract.

A team led by ICREA Research Professor Pia Cosma at the Centre for
Genomic Regulation (CRG) in Barcelona and funded by Fundacio' "la Caixa"
has now found that cell fusion events also take place in the human retina.

The researchers tested whether cell fusion events could differentiate
into cells that turn into neurons, which would show potential for tissue regeneration. The team fused Mu"ller glia, cells that play a secondary but important role in maintaining the structure and function of the retina,
with adult stem cells derived from human adipose tissue or bone marrow.

"We were able to carry out cell fusion invitro,creating hybrid cells.

Importantly, the process was more efficient in the presence of a chemical signal transmitted from the retina in response to damage, resulting in
rates of hybridisation increasing twofold. This gave us an important
clue for the role of cell fusion in the retina," says Sergi Bonilla, postdoctoral researcher at the CRG at the time of publication and first
author of the study.

The hybrid cells were injected into a growing retinal organoid, a model
that closely resembles the function of the human retina. The researchers
found that the hybrid cells successfully engrafted into the tissue and differentiated into cells that closely resemble ganglion cells, a type
of neuron essential for vision.

"Our findings are important because they show that the Mu"ller Glia in the human retina have the potential to regenerate neurons," says Pia Cosma.

"Salamanders and fish can repair damage caused to the retina thanks
to their Mu"ller glia, which differentiate into neurons that rescue
or replace damaged neurons. Mammalian Mu"ller glia have lost this
regenerative capacity, which means retinal damage or degradation can lead
to visual impairment for life. Our findings bring us one step closer to recovering this ability." The authors caution that much work remains to
be done before the development of any potential treatments. One of the
next steps is understanding why hybrid cells -- with four complete sets
of chromosomes -- don't result in chromosomal instability and cancer development. The authors of the study believe the retina may have a
mechanism regulating chromosome segregation similar to the liver, which contains tetraploid cells that act as a genetic reservoir, undergoing
mitosis in response to stress and injury.

The study was led by the Centre for Genomic Regulation in collaboration
with the Institute for Bioengineering of Catalonia (IBEC) and the
Barraquer Ophthalmology Center. The work is mainly funded by the
CaixaResearch Health Research Call from Fundacio' "la Caixa" awarded to
Pia Cosma (CRG), Nuria Montserrat (IBEC) and Justin Christopher D'Antin (Barrraquer). It is also funded by the European Union's FET-Open EcaBox project, Velux Stiftung, the Spanish Ministry of Science and Innovation
and the Catalan Agency for Management of University and Research (AGAUR).


========================================================================== Story Source: Materials provided by Center_for_Genomic_Regulation. Note: Content may be edited for style and length.


========================================================================== Journal Reference:
1. Sergi A`ngel Bonilla-Pons, Shoma Nakagawa, Elena Garreta Bahima,
A'lvaro
Ferna'ndez-Blanco, Martina Pesaresi, Justin Christopher D'Antin,
Ruben Sebastian-Perez, Daniela Greco, Eduardo Domi'nguez-Sala,
Rau'l Go'mez- Riera, Rafael Ignacio Barraquer Compte, Mara
Dierssen, Nuria Montserrat Pulido, Maria Pia Cosma. Mu"ller
glia fused with adult stem cells undergo neural differentiation
in human retinal models. eBioMedicine, 2022; 77: 103914 DOI:
10.1016/j.ebiom.2022.103914 ==========================================================================

Link to news story: https://www.sciencedaily.com/releases/2022/03/220315121418.htm

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