Huc‑MSCs‑derived exosomes attenuate inflammatory pain by regulating microglia pyroptosis and autophagy via the miR‑146a‑5p/TRAF6 axis

Journal of Nanobiotechnology, 2022 · DOI: 10.1186/s12951-022-01522-6 · Published: July 1, 2022

Simple Explanation

Chronic inflammatory pain diminishes life quality and lacks effective treatments. This study explores the therapeutic potential of human umbilical cord mesenchymal stem cells (huc-MSCs)-derived exosomes for CFA-induced inflammatory pain in mice. The study found that huc-MSCs-derived exosomes alleviated pain by increasing autophagy and inhibiting the activation of NLRP3 inflammasomes in the spinal cord, reducing neuroinflammation. The exosomes' therapeutic effect involves miR-146a-5p, which targets TRAF6, leading to increased autophagy and reduced pyroptosis (inflammatory cell death) in microglia, key immune cells in the spinal cord.

Study Duration

Not specified

Participants

C57BL/6J male mice, BV2 microglia cells, Huc-MSCs

Evidence Level

Not specified

Key Findings

1
Huc-MSCs-derived exosomes alleviated mechanical allodynia and thermal hyperalgesia in CFA-induced inflammatory pain model.
2
The exosomes inhibited NLRP3 inflammasome components and gasdermin D (GSDMD-F, GSDMD-N) in BV2 microglia cells, suggesting reduced pyroptosis.
3
Huc-MSCs-derived exosomes regulate autophagy and pyroptosis via miR-146a-5p/TRAF6 in vitro.

Research Summary

This study investigates the therapeutic effect of huc-MSCs-derived exosomes on CFA-induced inflammatory pain in mice. The exosomes were administered intrathecally, and behavioral tests were conducted to assess pain alleviation. The results demonstrate that huc-MSCs-derived exosomes reduce mechanical allodynia and thermal hyperalgesia, attenuating neuroinflammation by modulating autophagy and inhibiting NLRP3 inflammasome activation. The study identifies miR-146a-5p, enriched in the exosomes, as a key regulator targeting TRAF6, leading to increased autophagy and decreased pyroptosis, suggesting a novel therapeutic avenue for inflammatory pain.

Practical Implications

Therapeutic Potential

Huc-MSCs-derived exosomes show promise as a cell-free therapy for chronic inflammatory pain, offering an alternative to traditional treatments.

Targeted Approach

The miR-146a-5p/TRAF6 axis provides a specific target for developing therapies aimed at modulating microglia pyroptosis and autophagy.

Drug Development

The study supports the development of exosome-based therapeutics or drugs that mimic the effects of miR-146a-5p for pain management.

Study Limitations

1
The study primarily uses a mouse model, which may not fully represent human inflammatory pain conditions.
2
The in vitro experiments were conducted on BV2 microglia cells, which may not fully replicate the complexity of in vivo microglial responses.
3
Further research is needed to fully elucidate the long-term effects and potential side effects of huc-MSCs-derived exosome therapy.

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