Hypoxic-preconditioned mesenchymal stem cell-derived small extracellular vesicles promote the recovery of spinal cord injury by affecting the phenotype of astrocytes through the miR-21/JAK2/STAT3 pathway

Spinal cord injury (SCI) often leads to secondary damage, with neuroinflammation playing a significant role. This study explores the potential of using extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) that have been pre-conditioned in a low-oxygen environment (H-EVs) to promote SCI repair by influencing the behavior of astrocytes, a type of brain cell involved in inflammation. The researchers found that H-EVs are more effective than regular EVs in promoting motor function recovery, reducing cell death (apoptosis), and reducing inflammation after SCI. H-EVs also promoted a shift in astrocytes from a harmful (A1) phenotype to a beneficial (A2) phenotype. Further investigation revealed that H-EVs contain high levels of a molecule called miR-21, which influences astrocyte behavior by targeting a specific signaling pathway (JAK2/STAT3). This suggests that H-EVs exert their neuroprotective effects by delivering miR-21, leading to a shift in astrocyte phenotype and ultimately aiding in SCI repair.

• 1
  H-EVs are more effective than EVs in promoting motor function recovery, anti-apoptosis, and anti-inflammatory effects after SCI, both in vivo and in vitro.
• 2
  H-EV promoted the conversion of A1 astrocytes into A2 astrocytes more than EV.
• 3
  H-EV might affect astrocyte phenotypic alterations by delivering miR-21 targeting the JAK2/STAT3 signaling pathway.