Astrocyte-derived sEVs alleviate fibrosis and promote functional recovery after spinal cord injury in rats

Abstract

After spinal cord injury (SCI), there are complex pathological states in which the formation of scar tissues is a great obstacle to nerve repair. There are currently many potential treatments that can help to reduce the formation of glial scars. However, little attention has been paid to fibrous scarring. Astrocytes have neuroprotective effects on the central nervous system. Similar to other cells, they release small extracellular vesicles (sEVs). Astrocytes, pericytes, endothelial cells, and the basement membrane constitute the blood-spinal cord barrier. It can be seen that astrocytes are structurally closely related to pericytes that form fibrous scars. In this study, astrocyte-derived sEVs were injected into rats with SCI to observe the formation of fibrosis at the site of spinal cord injury. We found that astrocyte-derived sEVs can be ingested by pericytes in vitro and inhibit the proliferation and migration of pericytes. In vivo, astrocyte-derived sEVs could converge around the injury, promote tissue repair, and reduce fibrosis formation, thus promoting the recovery of limb function and improving walking ability. In conclusion, sEVs derived from astrocytes can reduce fibrosis and improve functional recovery after SCI, which provides a new possibility for the study of SCI.