HuMSC-EV induce monocyte/macrophage mobilization to orchestrate neovascularization in wound healing process following radiation injury

This study aims to investigate the mechanisms of human mesenchymal stem cell-derived extracellular vesicles (HuMSC-EV)-induced proangiogenic paracrine effects after radiation injury. HuMSC-EV were locally administered in mice hindlimb following 80-Gy X-ray irradiation and animals were monitored at different time points. HuMSC-EV improved neovascularization of the irradiated tissue, by stimulating angiogenesis, normalizing cutaneous blood perfusion, and increasing capillary density and production of proangiogenic factors. HuMSC-EV also stimulated vasculogenesis by promoting the recruitment and differentiation of bone marrow progenitors. Moreover, HuMSC-EV improved arteriogenesis by increasing the mobilization of monocytes from the spleen and the bone marrow and their recruitment into the muscle, with a pro-inflammatory potential. Importantly, monocyte depletion by clodronate treatment abolished the proangiogenic effect of HuMSC-EV. The critical role of Ly6C(hi) monocyte subset in HuMSC-EV-induced neovascularization process was further confirmed using Ccr2(-/-) mice. This study demonstrates that HuMSC-derived EV enhances the neovascularization process in the irradiated tissue by increasing the production of proangiogenic factors, promoting the recruitment of vascular progenitor cells, and the mobilization of innate cells to the injured site. These results support the concept that HuMSC-EV might represent a suitable alternative to stem cells for therapeutic neovascularization in tissue repair.

Automated summary

This study investigates the mechanisms by which human mesenchymal stem cell-derived extracellular vesicles (HuMSC-EV) promote angiogenesis and neovascularization after radiation injury. The study found that HuMSC-EV improved neovascularization of irradiated tissue by stimulating angiogenesis, increasing capillary density, and producing proangiogenic factors. HuMSC-EV also promoted vasculogenesis by recruiting and differentiating bone marrow progenitors. Furthermore, HuMSC-EV enhanced arteriogenesis by mobilizing monocytes and promoting their recruitment to the injured site. These findings suggest that HuMSC-EV could be a potential alternative to stem cells for therapeutic neovascularization in tissue repair.