{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,7]],"date-time":"2026-08-07T14:26:45Z","timestamp":1786112805745,"version":"build-2736575974"},"reference-count":53,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2026,5,9]],"date-time":"2026-05-09T00:00:00Z","timestamp":1778284800000},"content-version":"vor","delay-in-days":8,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T00:00:00Z","timestamp":1777593600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2022YFA1104900"],"award-info":[{"award-number":["2022YFA1104900"]}],"id":[{"id":"10.13039\/501100012166","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82200702"],"award-info":[{"award-number":["82200702"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J of Extracellular Vesicle"],"published-print":{"date-parts":[[2026,5]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>The role of human umbilical cord mesenchymal stem cell\u2010derived extracellular vesicles (hUCMSC\u2010EVs) in liver regeneration is promising, yet their clinical translation is hampered by insufficient production. Current strategies targeting their secretion are inefficient and lack a clear mechanistic understanding. We isolated and characterized hUCMSC\u2010EVs pretreated with the H89 and other mTORC1 inhibitors. Our findings revealed that H89 effectively enhances the secretion of hUCMSC\u2010EVs across diverse cell types, demonstrating universal efficacy. Importantly, H89 upregulates GABARAPL1 expression, a key negative regulator of the PKA\/mTORC1 pathway, to inhibit mTORC1 activity and promote the formation of amphisomes and SNARE\u2010mediated hUCMSC\u2010EVs release. Furthermore, EVs derived from H89\u2010pretreated hUCMSCs (H\u2010EVs) exhibited altered cargo composition, significantly increased proliferative activity, and potentiated liver regeneration via the RELA\/miR\u201029a axis, which regulates the homeostasis of hepatic stellate cells. Our results highlight that H89 enhances hUCMSC\u2010EV secretion through mTORC1 inhibition, with the resulting benefits for liver regeneration mediated by the RELA\/miR\u201029a network. These findings demonstrate the great promise of H89 in EV\u2010based liver regeneration, offering a promising platform for clinical translation.<\/jats:p>","DOI":"10.1002\/jev2.70285","type":"journal-article","created":{"date-parts":[[2026,5,10]],"date-time":"2026-05-10T06:04:16Z","timestamp":1778393056000},"source":"Crossref","is-referenced-by-count":1,"title":["The Small Molecule H89 Facilitates Mesenchymal Stem Cell\u2010derived Extracellular Vesicle Release and Optimizes Therapeutic Efficacy in Liver Regeneration"],"prefix":"10.1002","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0007-2633-9220","authenticated-orcid":false,"given":"Yu","family":"Fu","sequence":"first","affiliation":[{"name":"Department of Hepatobiliary Surgery II GuangDong Engineering Technology Research Center of Artificial Organ and Tissue Engineering Guangzhou Clinical Research and Transformation Center for Artificial Liver Institute of Regenerative Medicine General Surgery Center Zhujiang Hospital 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