Regenerative therapy · 2026
Extracellular vesicles subpopulation derived of clonal mesenchymal stem cells protected retinal ganglion cells in mouse model with optic nerve crush.
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Satarian Leila, Eslami Nasim, Saeedi-Fard Rezvaneh, Yektadoost Elham, Shojaei Amir, Hosseini Mazinani Fatemeh Sadat, Taghiyar Leila, Poosti Sara, Nazari Abdolreza, Zarei Fatemeh, Halvaie Majid, Shekari Faezeh
Аннотация
INTRODUCTION: Recent studies have shown that Mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) have significant potential to protect retinal ganglion cells (RGCs) function. Here, EVs were obtained from various MSCs, including dental pulp MSCs, trabecular meshwork MSCs, and bone marrow-derived clonal MSCs (cMSCs).
METHODS: The different fractions of EVs were separated by high-speed (20K) and ultra-speed (110K) centrifugation. The functionality of EVs was then assessed in a mouse model of optic nerve crush (ONC).
RESULTS: The result showed that all EVs derived from various MSC sources could improve the optomotor response in ONC mice. Visual behavior and retrograde tracing of RGCs showed that both subpopulations of EVs derived from cMSCs were efficient and had a higher survival rate in Brn3a-positive RGCs. The ratio of p-AKT/AKT and p-PI3K/PI3K increased, and the expression of procaspase and caspase decreased in the retina and optic nerve following treatment with 20K subpopulation of cMSC-EVs.
CONCLUSIONS: These results suggest that the increased restoration of visual behavior after cMSC-EV-20K treatment may be related to the protection of the RGCs by multi-trophic factors in EVs. Because the production of the EV-20K fraction is more accessible with fewer facilities, it has more capacity to be translated into the clinics for the repair of damaged optic nerves.
METHODS: The different fractions of EVs were separated by high-speed (20K) and ultra-speed (110K) centrifugation. The functionality of EVs was then assessed in a mouse model of optic nerve crush (ONC).
RESULTS: The result showed that all EVs derived from various MSC sources could improve the optomotor response in ONC mice. Visual behavior and retrograde tracing of RGCs showed that both subpopulations of EVs derived from cMSCs were efficient and had a higher survival rate in Brn3a-positive RGCs. The ratio of p-AKT/AKT and p-PI3K/PI3K increased, and the expression of procaspase and caspase decreased in the retina and optic nerve following treatment with 20K subpopulation of cMSC-EVs.
CONCLUSIONS: These results suggest that the increased restoration of visual behavior after cMSC-EV-20K treatment may be related to the protection of the RGCs by multi-trophic factors in EVs. Because the production of the EV-20K fraction is more accessible with fewer facilities, it has more capacity to be translated into the clinics for the repair of damaged optic nerves.