Cell Fusion Jump-starts Retinal Regeneration
Researchers have reported that they have successfully fused human retinal cells with adult stem cells, in a novel potential regenerative therapy to treat retinal damage and visual impairment.
The resulting hybrid cells stimulate the regenerative potential of human retinal tissue, something previously only thought to be found in cold-blood vertebrates.
Cell fusion events, where two different cells combine into one single entity, are known to be a possible mechanism contributing to tissue regeneration. These cell fusions result in four sets of chromosomes instead of the usual two. Though a rare phenomenon in humans, it has been reliably detected in the liver, brain, and gastrointestinal tract. Now, cell fusion events have been found also take place in the human retina, as reported in eBioMedicine.
Seeking to see if cell fusion events could differentiate into neurons, the researchers fused Müller glia, cells that play a secondary but important role in maintaining the structure and function of the retina, with adult stem cells.
“We were able to carry out cell fusion in vitro, 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,” said first author Sergi Bonilla.
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 Müller Glia in the human retina have the potential to regenerate neurons,” said lead researcher Professor Pia Cosma. “Salamanders and fish can repair damage caused to the retina thanks to their Müller glia, which differentiate into neurons that rescue or replace damaged neurons. Mammalian Müller 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.”
Further work will be to understand why these hybrid cells, which have 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.
Source: Center for Genomic Regulation
