Exosomes derived from plasma: promising immunomodulatory agents for promoting angiogenesis to treat radiation-induced vascular dysfunction.

Ionizing radiation (IR)-induced vascular disorders slow down tissue regeneration. Exosomes derived from plasma exhibit potential to promote angiogenesis; meanwhile, the immune microenvironment plays a significant role in the process. This study aimed to test the hypothesis that plasma exosomes promote angiogenesis in irradiated tissue by mediating the immune microenvironment. First, we explored the impact of IR on macrophages. We found that cell viability and capacity for promoting angiogenesis were decreased in irradiated macrophages compared to control macrophages. Then, we isolated and characterized rat plasma-derived exosomes (RP-Exos) which were defined as 40-160 nm extracellular vesicles extracted from rat plasma. Afterward, we evaluated the effects of RP-Exos on the behaviors of irradiated macrophages. Our results show that RP-Exos promoted cell proliferation. More importantly, we found that RP-Exos stimulated the immune microenvironment in a manner that improved the angiogenesis-related genes and proteins of irradiated macrophages. The supernatant of macrophage cell cultures was used as conditioned medium to treat human primary umbilical vein endothelial cells, further confirming the pro-angiogenic ability of macrophages receiving RP-Exo intervention. RP-Exos were used in vivo to treat irradiated skin or calvarial defects in irradiated Sprague-Dawley male rats. The results indicated the ability of RP-Exos to enhance angiogenesis and promote tissue regeneration. Our research suggested the potential of plasma exosomes to be used as immunomodulatory agents with angiogenic capacity to treat radiation-associated vascular disorders and facilitate tissue repair.