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Published on: March 30, 2018
Schwann cell-derived exosomes containing MFG-E8 modify macrophage/microglial polarization for attenuating
Jie Ren1, Bin Zhu1, Guangjin Gu1
1National Spinal Cord Injury International Cooperation Base, Tianjin Key Laboratory of Spine and Spinal Cord Injury, Department of Orthopedics, Tianjin Medical University General Hospital, Tianjin, China.
Abstract:
Macrophage/microglia polarization acts as an important part in regulating inflammatory responses in spinal cord injury (SCI). However, the regulation of inflammation of Schwann cell-derived exosomes (SCDEs) for SCI repair is still unclear. Therefore, we intend to find out the effect of SCDEs on regulating the inflammation related to macrophage polarization during the recovery of SCI. Firstly, the thesis demonstrated that SCDEs could attenuate the LPS- inflammation in BMDMs by suppressing M1 polarization and stimulating M2 polarization. Similarly, SCDEs improved functional recovery of female Wistar rats of the SCI contusion model according to BBB (Basso, Beattie, and Bresnahan) score, electrophysiological assay, and the gait analysis system of CatWalk XT. Moreover, MFG-E8 was verified as the main component of SCDEs to improve the inflammatory response by proteomic sequencing and lentiviral transfection. Improvement of the inflammatory microenvironment also inhibited neuronal apoptosis. The knockout of MFG-E8 in SCs can reverse the anti-inflammatory effects of SCDEs treatment. The SOCS3/STAT3 signaling pathway was identified to participate in upregulating M2 polarization induced by MFG-E8. In conclusion, our findings will enrich the mechanism of SCDEs in repairing SCI and provide potential applications and new insights for the clinical translation of SCDEs treatment for SCI.
Insights
Schwann cell-derived exosomes (SCDEs) reduce inflammation and improve functional recovery after spinal cord injury (SCI) by promoting M2 macrophage polarization. MFG-E8 is key to SCDEs
Area of Science:
- Neuroscience
- Regenerative Medicine
- Immunology
Background:
- Macrophage and microglia polarization are crucial in spinal cord injury (SCI) inflammation.
- The role of Schwann cell-derived exosomes (SCDEs) in modulating SCI-related inflammation is not fully understood.
Purpose of the Study:
- To investigate the effect of SCDEs on macrophage polarization and inflammation during SCI recovery.
- To identify the key component of SCDEs responsible for anti-inflammatory effects and elucidate the underlying mechanism.
Main Methods:
- In vitro studies using bone marrow-derived macrophages (BMDMs) to assess macrophage polarization.
- In vivo SCI contusion model in Wistar rats, evaluating functional recovery using BBB scores, electrophysiology, and CatWalk XT gait analysis.
- Proteomic sequencing and lentiviral transfection to identify and validate the role of MFG-E8.
- Investigation of the SOCS3/STAT3 signaling pathway.
Main Results:
- SCDEs suppressed M1 polarization and promoted M2 polarization in BMDMs, reducing LPS-induced inflammation.
- SCDEs significantly improved functional recovery in a rat SCI model.
- MFG-E8 was identified as a critical component of SCDEs mediating anti-inflammatory effects, with its knockout reversing SCDEs' benefits.
- The SOCS3/STAT3 pathway was implicated in mediating MFG-E8-induced M2 polarization.
- Reduced neuronal apoptosis was observed due to the improved inflammatory microenvironment.
Conclusions:
- SCDEs effectively attenuate inflammation and promote functional recovery in SCI by modulating macrophage polarization.
- MFG-E8 is a key functional component of SCDEs, orchestrating anti-inflammatory effects via the SOCS3/STAT3 pathway.
- These findings offer insights into the therapeutic mechanisms of SCDEs for SCI and support their clinical translation.
