MSC derived EV loaded with miRNA-22 inhibits the inflammatory response and nerve function recovery after spinal cord injury in rats
J Cell Mol Med, 2021 · DOI: 10.1111/jcmm.16965 · Published: September 19, 2021
Simple Explanation
Spinal cord injury (SCI) can cause severe dyskinesia and sensory disturbance. Inflammation caused by inflammatory factors can lead to secondary damage. The mechanism of inflammatory response of SCI is relatively complicated, involving both nerve cell injury and the participation of the immune system. Mesenchymal stem cells (MSCs) can repair the nerve function injury of SCI to a certain extent, promote the regeneration of nerve axons and enhance the repair of motor nerves as well as functional repair. However, the transplantation of MSCs may cause side effects such as tissue immune rejection, teratogenesis, and tumorigenesis EV are vesicle-like structures secreted by cells. Studies have found that the EV derived from MSCs also exert good effects on the nerve repair of SCI. In addition, MSC-derived EV greatly attenuate the various side effects caused by MSCs. Therefore, in this study, miRNA-22 was loaded into the MSC-derived EV, which was speculated to promote the regeneration of nerve cells and inhibit neuroinflammation, thereby playing a synergistic role.
Key Findings
- 1EV-miRNA-22 could inhibit the occurrence of pyroptosis in microglia, suppress the cell membrane pore opening, and inhibit the release of inflammatory factors and the expression of GSDMD.
- 2EV-miRNA-22 showed higher pyroptosis-inhibiting ability than EV. Consequently, EV-miRNA-22 could inhibit the nerve function injury after SCI in rats, inhibit the level of inflammatory factors in the tissue and the activation of microglia.
- 3miRNA-22-loaded MSCs-EV (EV-miRNA-22) could cooperate with EV to inhibit inflammatory response and nerve function repair after SCI.
Research Summary
Practical Implications
Therapeutic Potential
EV-miRNA-22 shows good therapeutic potentials for SCI mainly by cooperating with MSCs-EV, suggesting a new avenue for SCI treatment.
Inflammation Inhibition
The study highlights the importance of inhibiting inflammation, particularly pyroptosis, in managing SCI.
Microglia Modulation
Targeting microglia activation with EV-miRNA-22 can reduce inflammatory factors and improve nerve function recovery.
Study Limitations
- 1The study is conducted on rats, and results may not directly translate to humans.
- 2The exact mechanisms of cooperation between MSCs-EV and miRNA-22 require further investigation.
- 3Long-term effects of EV-miRNA-22 treatment on SCI recovery were not assessed.