Human PMSCs‑derived small extracellular vesicles alleviate neuropathic pain through miR‑26a‑5p/Wnt5a in SNI mice model

Journal of Neuroinflammation, 2022 · DOI: https://doi.org/10.1186/s12974-022-02578-9 · Published: September 1, 2022

Regenerative Medicine Immunology Pain Management

Simple Explanation

Mesenchymal stem cell (MSCs)-derived small Extracellular Vesicles (sEVs) are considered a new cell-free therapy for nerve injury pain, but it's unknown if human placental MSC-derived sEVs relieve sciatic nerve injury pain and how. This study investigates hPMSCs-derived sEVs' roles and mechanisms in neuropathic pain. The spared nerve injury (SNI) mouse model was employed. Intrathecal injection of sEVs or miR-26a-5p agomir was performed on the seventh day of modeling, to study its anti-nociceptive effect. The study reported that hPMSCs derived sEVs are a promising therapy for nerve injury induced neuropathic pain. In addition, it showed that the miR-26a-5p in the sEVs regulated Wnt5a/Ryk/CaMKII/NFAT partly take part in the analgesia through anti-neuroinflammation.

Study Duration

Not specified

Participants

Male C57/BL6 mice (8 weeks, 22 ± 2 g)

Evidence Level

Not specified

Key Findings

1
A single intrathecal injection of sEVs durably reversed mechanical hypersensitivity in the left hind paw of mice with partial sciatic nerve ligation.
2
Intrathecal injection of miR-26a-5p agomir, the second high counts microRNA in hPMSCs derived sEVs, significantly suppressed neuropathic pain and neuroinflammation in SNI mice.
3
hPMSCs derived sEVs as a promising therapy for nerve injury induced neuropathic pain.

Research Summary

This study investigates the potential of human placental mesenchymal stem cell-derived small extracellular vesicles (hPMSCs-derived sEVs) to alleviate neuropathic pain in a spared nerve injury (SNI) mouse model. The study demonstrates that a single intrathecal injection of hPMSCs-derived sEVs can durably reverse mechanical hypersensitivity in SNI mice, with the sEVs localizing in neurons and microglia in the spinal cord. The research identifies miR-26a-5p, a microRNA enriched in hPMSCs-derived sEVs, as a key regulator in this process, targeting Wnt5a and influencing the Wnt signaling pathway to achieve analgesia through anti-neuroinflammation.

Practical Implications

Therapeutic Potential

hPMSCs-derived sEVs may represent a novel cell-free therapeutic approach for managing neuropathic pain.

Target Identification

miR-26a-5p and its downstream target Wnt5a provide specific targets for developing future pain therapies.

Drug Delivery

SEVs can be explored as targeted drug carriers because of their strong homing ability.

Study Limitations

1
The study is conducted on mice, and the results may not directly translate to humans.
2
The exact mechanisms of sEV uptake and action require further investigation.
3
The study did not explore the long-term effects and potential side effects of sEV treatment.

Your Feedback

Was this summary helpful?

Back to Regenerative Medicine