hUCMSC-derived exosomes mitigate blood-spinal cord barrier disruption by activating AMPK/mTOR-mediated autophagic flux after acute spinal cord injury

Abstract

After spinal cord injury (SCI), the integrity of the blood-spinal cord barrier (BSCB) can be disrupted, leading to the secondary injuries such as inflammatory cell infiltration, neuronal death, and spinal cord hematoma. It is important to maintain the integrity of the BSCB to help restore function following SCI. While some studies have demonstrated the therapeutic effects of exosomes derived from human umbilical cord mesenchymal stem cells (hUCMSC-exos), their role in preserving BSCB integrity remains unclear. In our study, we demonstrated the protective effects of hUCMSC-exos on the BSCB and its mechanism. The results of this study indicate that hUCMSC-exos promote motor function recovery, preserve spinal cord structure, and reduce neuronal loss by inhibiting BSCB leakage following SCI. Experimental investigations conducted in vivo and in vitro have demonstrated that hUCMSC-exos can mitigate the loss of adherens junctions (AJs) and tight junctions (TJs) and stimulate autophagy in spinal cord endothelial cells. The protective effects were also found to be significantly reversed following the inhibition of autophagy using 3-MA. In conclusion, our study demonstrates that hUCMSC-exos protect the integrity of BSCB by promoting the repair of spinal endothelial cells through activation of autophagy, thereby exerting a protective role in SCI.