{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T22:16:37Z","timestamp":1790720197027,"version":"4.1.0"},"reference-count":101,"publisher":"MDPI AG","issue":"7","license":[{"start":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T00:00:00Z","timestamp":1743552000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Key R&amp;D Program of China","award":["2023YFC3605100"],"award-info":[{"award-number":["2023YFC3605100"]}]},{"name":"National Key R&amp;D Program of China","award":["82472621"],"award-info":[{"award-number":["82472621"]}]},{"name":"National Key R&amp;D Program of China","award":["82171422"],"award-info":[{"award-number":["82171422"]}]},{"name":"National Natural Science Foundation of China","award":["2023YFC3605100"],"award-info":[{"award-number":["2023YFC3605100"]}]},{"name":"National Natural Science Foundation of China","award":["82472621"],"award-info":[{"award-number":["82472621"]}]},{"name":"National Natural Science Foundation of China","award":["82171422"],"award-info":[{"award-number":["82171422"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Peripheral nerve injury (PNI) remains a significant clinical challenge, often leading to long-term functional impairment. Despite advances in therapies, current repair strategies offer unsatisfactory clinical outcomes. Exosomes derived from induced pluripotent stem cells (iPSC-Exos) have emerged as a promising therapeutic approach in regenerative medicine. This study assesses the efficacy and safety of iPSC-Exos in a rat model of sciatic nerve crush injury. Briefly, iPSCs were generated from peripheral blood mononuclear cells (PBMCs) of healthy donors using Sendai virus vectors and validated for pluripotency. iPSC-Exos were characterized and injected at the injury site. Functional recovery was assessed through gait analysis, grip strength, and pain response. Histological and molecular analyses were used to examine axonal regeneration, myelination, Schwann cell (SC) activation, angiogenesis, and changes in gene expression. iPSC-Exos were efficiently internalized by SC, promoting their proliferation. No adverse effects were observed between groups on body weight, organ histology, or hematological parameters. iPSC-Exos injection significantly enhanced nerve regeneration, muscle preservation, and vascularization, with RNA sequencing revealing activation of PI3K-AKT and focal adhesion pathways. These findings support iPSC-Exos as a safe and effective non-cell-based therapy for PNIs, highlighting their potential for clinical applications in regenerative medicine.<\/jats:p>","DOI":"10.3390\/cells14070529","type":"journal-article","created":{"date-parts":[[2025,4,2]],"date-time":"2025-04-02T05:43:33Z","timestamp":1743572613000},"page":"529","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":16,"title":["Induced Pluripotent Stem Cell-Derived Exosomes Promote Peripheral Nerve Regeneration in a Rat Sciatic Nerve Crush Injury Model: A Safety and Efficacy Study"],"prefix":"10.3390","volume":"14","author":[{"given":"Fatima","family":"Aldali","sequence":"first","affiliation":[{"name":"Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0006-2971-2433","authenticated-orcid":false,"given":"Yujie","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5533-6009","authenticated-orcid":false,"given":"Chunchu","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangling","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojian","family":"Cao","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jia","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajie","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianlin","family":"Ding","sequence":"additional","affiliation":[{"name":"Department of Gynecology & Obstetrics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hong","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Rehabilitation Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030, China"},{"name":"Stem Cell Research Center, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430000, China"},{"name":"Hubei Key Laboratory of Neural Injury and Functional Reconstruction, Huazhong University of Science and Technology, Wuhan 430030, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,4,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"780","DOI":"10.1002\/jnr.24538","article-title":"Peripheral nerve injury and myelination: Potential therapeutic strategies","volume":"98","author":"Modrak","year":"2020","journal-title":"J. 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