Schwann cell-derived exosomes containing MFG-E8 modify macrophage/microglial polarization for attenuating inﬂammation via the SOCS3/STAT3 pathway after spinal cord injury

Cell Death and Disease, 2023 · DOI: 10.1038/s41419-023-05607-4 · Published: January 19, 2023

Simple Explanation

Spinal cord injury (SCI) can cause severe motor, sensory, and autonomic nerve dysfunction. Therapies that influence inflammatory cascades are likely to benefit functional recovery after SCI. Exosomes, small vesicles containing active molecules, play a crucial role in intercellular communication. Schwann cell-derived exosomes (SCDEs) can promote axonal regeneration and suppress inflammation, indicating broad application prospects for SCI. This study analyzes whether SCDEs exert an anti-inflammatory effect by inhibiting M1 polarization and promoting M2 polarization of macrophage/microglia, thus promoting functional recovery after SCI.

Study Duration

28 days

Participants

200 adult female Wistar rats

Evidence Level

Not specified

Key Findings

1
SCDEs attenuate LPS-induced inflammation in BMDMs by suppressing M1 polarization and stimulating M2 polarization, improving functional recovery in SCI rats.
2
MFG-E8, a key component of SCDEs, improves the inflammatory response, inhibits neuronal apoptosis, and upregulates M2 polarization via the SOCS3/STAT3 signaling pathway.
3
Knockout of MFG-E8 in SCs reverses the anti-inflammatory effects and M2 polarization of macrophage/microglia caused by SCDEs treatment.

Research Summary

This study demonstrates that SCDEs can attenuate the inflammatory response by regulating macrophage/microglia polarization, reducing neuronal apoptosis, and promoting functional recovery after SCI. MFG-E8 is identified as the key component of SCDEs in improving inflammation. KO of MFG-E8 can partly reverse the anti-inflammatory effects and promote M2 polarization of macrophage/microglia via the SOCS3/STAT3 signaling pathway. The findings enrich the anti-inflammatory mechanism of SCDEs treatment in repairing SCI and provide a new potential and therapeutic option for repairing SCI.

Practical Implications

Therapeutic Potential for SCI

SCDEs offer a potential therapeutic approach for spinal cord injury by modulating inflammation and promoting functional recovery.

Targeted Anti-Inflammatory Strategies

MFG-E8 within SCDEs can be targeted to enhance anti-inflammatory effects and promote M2 macrophage polarization in SCI treatment.

Clinical Translation of SCDEs

The study provides new insights for the clinical translation of SCDE treatment for SCI, focusing on the role of MFG-E8 and the SOCS3/STAT3 pathway.

Study Limitations

1
The research mainly focused on the inflammation modulation of SCDEs for SCI treatment without analyzing the neural proliferation and differentiation and axonal regeneration.
2
The study has only confirmed that MFG-E8 can induce M2 polarization without exploring the multiple activated M2 subtypes, including M2a, M2b, and M2c.
3
Further studies involved in knockout rats/mice are required to verify the above findings, since only shRNAs were used to knock out MFG-E8 in our study.

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