Gessica S. A. Silva, Afrânio F. Evangelista, Girlaine C. Santos, Thaís A. Santana, Luiza C. F. Opretzka, Pedro S. S. Lauria, Marco A. Stimamiglio, Milena B. P. Soares, Cristiane F. Villarreal
Diabetic sensory neuropathy (DSN) is a debilitating complication of diabetes. Extracellular vesicles derived from mesenchymal stem cells (EV-BMC) that contain bioactive molecules may aid in the management of neuropathy. EV-BMCS are isolated and characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). DSN is induced in C57BL/6 mice using streptozotocin; mechanical nociceptive thresholds are measured over 92 days. Thirty days post-induction, mice received intravenous vehicle, EV-BMSC (100 µL), or BMSC (1 × 106 cells). Involvement of the opioid system is tested using naloxone (5 mg kg−1) at 7, 30, and 60 days post-treatment. RT-qPCR assessed preproenkephalin expression in the spinal cord and BMSC culture supernatant. EV-BMSC vesicles ranged from 52.4 to 450 nm and had typical EV morphology, with a total of 4.4 × 108 vesicles recovered from 1 × 106 BMSC. Both BMSC and EV-BMSC treatments reversed neuropathy signs (p < 0.05). Naloxone reversed these antinociceptive effects (p < 0.05). RT-qPCR showed that EV-BMSC increased preproenkephalin expression at 7 days (p < 0.001) and 60 days (p < 0.01), while BMSC only increased expression at 7 days (p < 0.001). EVs from BMSC preserved the antinociceptive effects of the parent cells, likely via the endogenous opioid system, suggesting the potential of cell-free therapies for managing DSN.
{"title":"Extracellular Vesicles Derived From Mesenchymal Bone Marrow Cells Promote Antinociception in a Murine Model of Diabetic Neuropathy via the Endogenous Opioid System","authors":"Gessica S. A. Silva, Afrânio F. Evangelista, Girlaine C. Santos, Thaís A. Santana, Luiza C. F. Opretzka, Pedro S. S. Lauria, Marco A. Stimamiglio, Milena B. P. Soares, Cristiane F. Villarreal","doi":"10.1002/adtp.202500195","DOIUrl":"https://doi.org/10.1002/adtp.202500195","url":null,"abstract":"<p>Diabetic sensory neuropathy (DSN) is a debilitating complication of diabetes. Extracellular vesicles derived from mesenchymal stem cells (EV-BMC) that contain bioactive molecules may aid in the management of neuropathy. EV-BMCS are isolated and characterized using transmission electron microscopy (TEM) and nanoparticle tracking analysis (NTA). DSN is induced in C57BL/6 mice using streptozotocin; mechanical nociceptive thresholds are measured over 92 days. Thirty days post-induction, mice received intravenous vehicle, EV-BMSC (100 µL), or BMSC (1 × 10<sup>6</sup> cells). Involvement of the opioid system is tested using naloxone (5 mg kg<sup>−1</sup>) at 7, 30, and 60 days post-treatment. RT-qPCR assessed preproenkephalin expression in the spinal cord and BMSC culture supernatant. EV-BMSC vesicles ranged from 52.4 to 450 nm and had typical EV morphology, with a total of 4.4 × 10<sup>8</sup> vesicles recovered from 1 × 10<sup>6</sup> BMSC. Both BMSC and EV-BMSC treatments reversed neuropathy signs (<i>p</i> < 0.05). Naloxone reversed these antinociceptive effects (<i>p</i> < 0.05). RT-qPCR showed that EV-BMSC increased preproenkephalin expression at 7 days (<i>p</i> < 0.001) and 60 days (<i>p</i> < 0.01), while BMSC only increased expression at 7 days (<i>p</i> < 0.001). EVs from BMSC preserved the antinociceptive effects of the parent cells, likely via the endogenous opioid system, suggesting the potential of cell-free therapies for managing DSN.</p>","PeriodicalId":7284,"journal":{"name":"Advanced Therapeutics","volume":"9 1","pages":""},"PeriodicalIF":2.6,"publicationDate":"2026-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://advanced.onlinelibrary.wiley.com/doi/epdf/10.1002/adtp.202500195","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"146096589","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}