{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,27]],"date-time":"2026-07-27T09:59:54Z","timestamp":1785146394725,"version":"3.55.0"},"reference-count":58,"publisher":"Wiley","issue":"6","license":[{"start":{"date-parts":[[2026,6,16]],"date-time":"2026-06-16T00:00:00Z","timestamp":1781568000000},"content-version":"vor","delay-in-days":15,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,6,1]],"date-time":"2026-06-01T00:00:00Z","timestamp":1780272000000},"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":["2022YFA1106800"],"award-info":[{"award-number":["2022YFA1106800"]}],"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":["32471211"],"award-info":[{"award-number":["32471211"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["T2121004"],"award-info":[{"award-number":["T2121004"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82302726"],"award-info":[{"award-number":["82302726"]}],"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":[[2026,6]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Tendon repair remains a substantial clinical problem with limited treatment options. While Nestin\n                    <jats:sup>+<\/jats:sup>\n                    tendon stem\/progenitor cells (TSPCs) are known to regulate tendon healing, their clinical translation faces challenges. Here, we show that exosomes derived from engineered Nestin\u2010overexpressing TSPCs (Nes\u2010EVs) significantly ameliorate tendinopathy in multiple mouse models. We isolated Nes\u2010EVs following lentiviral Nestin overexpression and demonstrated their capacity to reduce cellular senescence and promote tenogenic differentiation in vitro. In collagenase\u2010induced (WT and\n                    <jats:italic>\n                      Nes\u2010Cre\n                      <jats:sup>ERT2<\/jats:sup>\n                      ;iDTR\n                    <\/jats:italic>\n                    ) and naturally aged murine tendinopathy models, Nes\u2010EVs robustly restored motor function, improved tissue architecture, reduced senescence markers and restored collagen homeostasis. Integrated transcriptomic and metabolomic profiling revealed a hallmark enrichment of the pantothenate and CoA biosynthesis pathway in both Nestin\n                    <jats:sup>+<\/jats:sup>\n                    TSPCs and their exosomes. Mechanistically, Nes\u2010EVs enhanced mitochondrial function in tenocytes, increasing ATP production and diminishing oxidative stress thereby revitalizing cellular metabolism in damaged tendons. Our findings unveil a fundamental mechanism where Nes\u2010EVs coordinate tendon metabolism and homeostasis, offering a promising acellular therapeutic strategy for tendinopathy.\n                  <\/jats:p>","DOI":"10.1002\/jev2.70318","type":"journal-article","created":{"date-parts":[[2026,6,17]],"date-time":"2026-06-17T06:51:18Z","timestamp":1781679078000},"source":"Crossref","is-referenced-by-count":0,"title":["Engineered Nestin\n                    <sup>+<\/sup>\n                    TSPC\u2010Derived Exosomes Promote Tendon Repair Via Metabolic Reprogramming"],"prefix":"10.1002","volume":"15","author":[{"given":"Linxiang","family":"Cheng","sequence":"first","affiliation":[{"name":"Department of Orthopedic Surgery of Sir Run Run Shaw Hospital, and Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province  Hangzhou Zhejiang PR China"},{"name":"State Key Laboratory of Transvascular Implantation Devices  Hangzhou PR China"},{"name":"Spine lab, Department of Orthopaedic Surgery, The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyu","family":"Guo","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine &amp; Orthopedic Surgery, The Second Affiliated Hospital, and Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province  Hangzhou Zhejiang PR China"},{"name":"State Key Laboratory of Transvascular Implantation Devices  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junshu","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine &amp; Orthopedic Surgery, The Second Affiliated Hospital, and Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province  Hangzhou Zhejiang PR China"},{"name":"State Key Laboratory of Transvascular Implantation Devices  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qiangqiang","family":"Zheng","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province  Hangzhou Zhejiang PR China"},{"name":"State Key Laboratory of Transvascular Implantation Devices  Hangzhou PR China"},{"name":"Spine lab, Department of Orthopaedic Surgery, The First Affiliated Hospital Zhejiang University School of Medicine  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhixiong","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery of Sir Run Run Shaw Hospital, and Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province  Hangzhou Zhejiang PR China"},{"name":"State Key Laboratory of Transvascular Implantation Devices  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jingyao","family":"Chen","sequence":"additional","affiliation":[{"name":"Core Facilities Zhejiang University School of Medicine  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jinhan","family":"Zhang","sequence":"additional","affiliation":[{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Sports Medicine &amp; Orthopedic Surgery, The Second Affiliated Hospital, and Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province  Hangzhou Zhejiang PR China"},{"name":"State Key Laboratory of Transvascular Implantation Devices  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2892-8962","authenticated-orcid":false,"given":"Zi","family":"Yin","sequence":"additional","affiliation":[{"name":"Department of Orthopedic Surgery of Sir Run Run Shaw Hospital, and Liangzhu Laboratory Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Dr. Li Dak Sum &amp; Yip Yio Chin Center for Stem Cells and Regenerative Medicine Zhejiang University School of Medicine  Hangzhou PR China"},{"name":"Key Laboratory of Motor System Disease Research and Precision Therapy of Zhejiang Province  Hangzhou Zhejiang PR China"},{"name":"State Key Laboratory of Transvascular Implantation Devices  Hangzhou PR China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,16]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1080\/14656566.2020.1763306"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11999-008-0260-1"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells8020166"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00018-018-2794-z"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm1630"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202507759"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.1002\/mco2.70095"},{"key":"e_1_2_10_9_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.aay9526"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jot.2024.09.003"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2014.08.020"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2019.09.007"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2020.06.004"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2021.02.008"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.014118"},{"key":"e_1_2_10_16_1","article-title":"Tendinopathy: The Interplay Between Mechanical Stress, Inflammation, and Vascularity","volume":"12","author":"Gehwolf R.","year":"2025","journal-title":"Advance Science"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-024-61399-3"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1177\/1071100713475353"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.3892\/ijmm.2015.2413"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1002\/advs.202206439"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/sms.13734"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/jev2.70198"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aau6977"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jmb.2015.09.019"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1600-0838.2009.00949.x"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1136\/bjsports-2016-097347"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2025.03.011"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms242015183"},{"key":"e_1_2_10_29_1","article-title":"Exosome Processing and Characterization Approaches for Research and Technology Development","volume":"9","author":"Lai J. 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