Effective treatment of optic neuropathies by intraocular delivery of MSC-sEVs through augmenting the G-CSF-macrophage pathway
Year: 2024
Type: article
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 Ly6C low monocytes/monocyte-derived macrophages (Mo/MΦ). Intravitreal administration of G-CSF, a clinically proven agent for treating neutropenia, or donor Ly6C low Mo/MΦ markedly improved neurological outcomes in vivo. Together, our data define a unique mechanism of MSC-sEV-induced G-CSF-to-Ly6C low Mo/MΦ signaling in repairing optic nerve injury and highlight local delivery of MSC-sEVs, G-CSF, and Ly6C low Mo/MΦ as therapeutic paradigms for the treatment of optic neuropathies.
Authors: Wei Yi, Ying Xue, Wenjie Qing, Yingxue Cao, Lingli Zhou, Mingming Xu, Zehui Sun, Yuying Li, Xiaomei Mai, Le Shi, Chang He, Feng Zhang, Elia J. Duh, Yihai Cao, Xialin Liu
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Funders: Swedish Cancer Foundation, National Natural Science Foundation of China, Karolinska Institutet, Novo Nordisk, Vetenskapsrådet, Guangdong Science and Technology Department, Novo Nordisk Fonden, Guangzhou Science, Technology and Innovation Commission, HORIZON EUROPE Framework Programme, Guangzhou Municipal Science and Technology Project, National Key Research and Development Program of China
Awards: Angiogenesis in diseases: mechanisms and therapeutic challenges, G132761758, Mechanistic study of the vasculature-modulated tumor microenvironment in tumor growth, metastasis and drug responses, G1783173773, G2295516037, G2731423936, G3221332791, Implementation of a zebrafish cancer model in diagnosis of human cancer invasion and prediction of drug responses, G4414717240, G5185431606, G6723881891, G7290188812, G8479057729
OpenAlex ID: W4391343555