ArticleJournal of neuroinflammation2022
Human PMSCs-derived small extracellular vesicles alleviate neuropathic pain through miR-26a-5p/Wnt5a in SNI mice model.
Article in Journal of neuroinflammation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers, 2 of them syntheses that pooled it.
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Who cites it
31 citing papers in PubMed, 2 syntheses or guidelines pooled it, 50 citations in OpenAlex.
- A Systematic Review of Stem Cell Secretome-Derived Exosomes for Neuropathic Pain: Therapeutic Mechanisms and Translational Potential.Molecular neurobiology · 2026Pooled it
- Systematic Review: Preclinical and Clinical Evidence on MSC Efficacy and Mechanism of Action in Neuropathic Pain Reduction.International journal of molecular sciences · 2026Pooled it
- Advances in the clinical application of mesenchymal stem cells for neurological disorders.Stem cell research & therapy · 2026Review
- Extracellular vesicles and their cargo molecules for peripheral nerve injuries and neuropathies: The composition, properties, and impact.Molecular aspects of medicine · 2026Review
- Recent advances in nanomaterial-based strategies for chronic pain alleviation.Materials today. Bio · 2026Review
- [miR-143-3p alleviates neuropathic pain in mice with spared nerve injury by targeting the KRAS/RalA pathway and inhibiting astrocyte activation].Nan fang yi ke da xue xue bao = Journal of Southern Medical University · 2026Article
- Review
- Mesenchymal stem cells and secretome as modulators of neuroinflammation in neurological disorders.Journal of translational medicine · 2026Review
- Therapeutic applications of mesenchymal stem cell-derived extracellular vesicles in pain management: A narrative review of emerging evidence and future directions.World journal of stem cells · 2026Review
- Sez6l promotes neuropathic pain via Wnt5a/CaFrontiers in genetics · 2026Article
- Mechanical cues as immunomodulators in neuroinflammation-driven spinal sensitization: analgesic mechanisms and therapeutic strategies.Frontiers in immunology · 2026Review
- TNF-α-preconditioning enhances analgesic efficacy of mesenchymal stem cell-derived extracellular vesicle in neuropathic painBioactive materials · 2025Article
- Advances in locally administered nucleic acid therapeutics.Bioactive materials · 2025Review
- Resolvin D1 accelerates resolution of neuroinflammation by inhibiting microglia activation through the BDNF/TrkB signaling pathway.European journal of medical research · 2025Article
- Bridging bioengineering and nanotechnology: Bone marrow derived mesenchymal stem cell-exosome solutions for peripheral nerve injury.World journal of stem cells · 2025Article
- Stem Cell-Derived Extracellular Vesicle-Mediated Therapeutic Signaling in Spinal Cord Injury.International journal of molecular sciences · 2025Review
- Extracellular Vesicles: A Review of Their Therapeutic Potentials, Sources, Biodistribution, and Administration Routes.International journal of nanomedicine · 2025Review
- From arthritis to central sensitization: targeting the neuro-immune axis via microglial modulation in acupuncture treatment for Juvenile Idiopathic Arthritis-associated pain.Frontiers in immunology · 2025Review
- miRNA packaging into small extracellular vesicles and implications in pain.Pain reports · 2024Review
- The Nociceptor Primary Cilium Contributes to Mechanical Nociceptive Threshold and Inflammatory and Neuropathic Pain.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundMesenchymal stem cell (MSCs)-derived small Extracellular Vesicles (sEVs) are considered as a new cell-free therapy for pain caused by nerve injury, but whether human placental mesenchymal stem cell-derived sEVs relieve pain in sciatic nerve injury and its possible mechanism are still unclear. In this study, we investigated the roles of hPMSCs-derived sEVs and related mechanisms in neuropathic pain.
methodsThe 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. sEVs' miRNA sequencing (miRNA-Seq) and bioinformatics analysis were performed to study the downstream mechanisms of miRNAs. RT-qPCR, protein assay and immunofluorescence were used for further validation.
resultsA single intrathecal injection of sEVs durably reversed mechanical hypersensitivity in the left hind paw of mice with partial sciatic nerve ligation. Immunofluorescence studies found that PKH26-labeled sEVs were visible in neurons and microglia in the dorsal horn of the ipsilateral L4/5 spinal cord and more enriched in the ipsilateral. According to miRNA-seq results, we found that 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. Bioinformatics analysis and dual-luciferase reporter gene analysis identified Wnt5a as a direct downstream target gene of miR-26a-5p. The results showed that overexpression of miR-26a-5p in vivo could significantly reduce the expression level of Wnt5a. In addition, Foxy5, a mimetic peptide of Wnt5a, can significantly reverse the inhibitory effect of miR-26a-5p on neuroinflammation and neuropathic pain, and at the same time, miR-26a-5p can rescue the effect of Foxy5 by overexpression.
conclusionsWe reported that hPMSCs derived sEVs as a promising therapy for nerve injury induced neuropathic pain. In addition, we showed that the miR-26a-5p in the sEVs regulated Wnt5a/Ryk/CaMKII/NFAT partly take part in the analgesia through anti-neuroinflammation, which suggests an alleviating pain effect through non-canonical Wnt signaling pathway in neuropathic pain model in vivo.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.