{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,20]],"date-time":"2026-09-20T07:53:34Z","timestamp":1789890814234,"version":"4.0.1"},"reference-count":80,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2025,12,16]],"date-time":"2025-12-16T00:00:00Z","timestamp":1765843200000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100004826","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["7252300"],"award-info":[{"award-number":["7252300"]}],"id":[{"id":"10.13039\/501100004826","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["advanced.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Adv Healthcare Materials"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The early imbalance in the inflammatory microenvironment (IME) following peripheral nerve injury (PNI) poses a major impediment to nerve regeneration. This study elucidates the mechanism through which human umbilical cord mesenchymal stem cell\u2010derived apoptotic microvesicles (HUCMSC\u2010Apo\u2010mvs) facilitate peripheral nerve repair via IME modulation. Comparative proteomics and miRNA sequencing analyses are conducted to identify compositional differences between exosomes (Exos) and Apoptotic microvesicles (Apo\u2010mvs) originating from the same parental HUCMSC. Early administration of HUCMSC\u2010Apo\u2010mvs at the transection injury site induced substantial macrophage recruitment. Contrary to Exos, Apo\u2010mvs significantly inhibited pro\u2010inflammatory M1\u2010type macrophage polarization while promoting their transition to the anti\u2010inflammatory M2\u2010type phenotype. This shift is accompanied by an enhanced secretion of anti\u2010inflammatory cytokines [Interleukin 10 (IL\u201010) and vascular endothelial growth factor (VEGF)], improved local angiogenesis, and the consequent alleviation of tissue hypoxia and neuroinflammation. Both Apo\u2010mvs and Exos enhanced Schwann cell (SC) migration and proliferation, thereby accelerating axonal regeneration and myelin remodeling. Animal studies further revealed that HUCMSC\u2010Apo\u2010mvs markedly improved early\u2010stage sciatic nerve regeneration, with long\u2010term functional recovery comparable to autologous nerve grafts. To the best of our knowledge, this is the first study to demonstrate the differential components between mesenchymal stem cell (MSC)\u2010derived Exos and Apo\u2010mvs, as well as their potential novel application in combination with acellular allogeneic nerve grafts for early inflammatory regulation in PNI. We hope that our findings will provide an experimental basis for the clinical translation of cell\u2010free tissue engineering approaches in MSC\u2010mediated peripheral nerve regeneration.<\/jats:p>","DOI":"10.1002\/adhm.202504087","type":"journal-article","created":{"date-parts":[[2025,12,17]],"date-time":"2025-12-17T06:16:51Z","timestamp":1765952211000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Mesenchymal Stem Cell\u2010Derived Apoptotic Micro\u2010Vesicles Repaired Sciatic Nerve Defect by Regulating Early Inflammatory Microenvironment and Promoting Angiogenesis"],"prefix":"10.1002","volume":"15","author":[{"given":"Haolin","family":"Liu","sequence":"first","affiliation":[{"name":"Institute of Orthopedics The Fourth Medical Center of Chinese PLA General Hospital Beijing Key Lab of Regenerative Medicine in Orthopedics Key Laboratory of Musculoskeletal Trauma &amp; War Injuries PLA  Beijing P. R. 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