Effective treatment of optic neuropathies by intraocular delivery of MSC-sEVs through augmenting the G-CSF-macrophage pathway.
Proc Natl Acad Sci U S A
; 121(6): e2305947121, 2024 Feb 06.
Article
em En
| MEDLINE
| ID: mdl-38289952
ABSTRACT
Optic neuropathies, characterized by injury of retinal ganglion cell (RGC) axons of the optic nerve, cause incurable blindness worldwide. Mesenchymal stem cell-derived small extracellular vesicles (MSC-sEVs) represent a promising "cell-free" therapy for regenerative medicine; however, the therapeutic effect on neural restoration fluctuates, and the underlying mechanism is poorly understood. Here, we illustrated that intraocular administration of MSC-sEVs promoted both RGC survival and axon regeneration in an optic nerve crush mouse model. Mechanistically, MSC-sEVs primarily targeted retinal mural cells to release high levels of colony-stimulating factor 3 (G-CSF) that recruited a neural restorative population of Ly6Clow monocytes/monocyte-derived macrophages (Mo/MΦ). Intravitreal administration of G-CSF, a clinically proven agent for treating neutropenia, or donor Ly6Clow Mo/MΦ markedly improved neurological outcomes in vivo. Together, our data define a unique mechanism of MSC-sEV-induced G-CSF-to-Ly6Clow Mo/MΦ signaling in repairing optic nerve injury and highlight local delivery of MSC-sEVs, G-CSF, and Ly6Clow Mo/MΦ as therapeutic paradigms for the treatment of optic neuropathies.
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Base de dados:
MEDLINE
Assunto principal:
Traumatismos do Nervo Óptico
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Células-Tronco Mesenquimais
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Vesículas Extracelulares
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article