{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T14:01:50Z","timestamp":1790863310670,"version":"4.1.0"},"reference-count":49,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2026,9,19]],"date-time":"2026-09-19T00:00:00Z","timestamp":1789776000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100012166","name":"National Key Research and Development Program of China","doi-asserted-by":"publisher","award":["2021YFA1101500"],"award-info":[{"award-number":["2021YFA1101500"]}],"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":["92049119"],"award-info":[{"award-number":["92049119"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["92049119"],"award-info":[{"award-number":["92049119"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"Joint Fund Project of Hubei Provincial Natural Science Foundation","award":["2025AFD323"],"award-info":[{"award-number":["2025AFD323"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Age-related degeneration remains a premier biomedical challenge, frequently underpinned by cellular senescence and stem cell dysfunction. Accumulating evidence suggests that umbilical cord mesenchymal stromal cell (UC-MSC)-derived extracellular vesicles (UC-EVs) and the longevity protein Klotho hold great promise as anti-aging biotherapeutics. Here, we strategically engineered UC-MSCs to overexpress Klotho and generated functional Klotho-enriched UC-EVs (KL-EVs). Our data demonstrated that genetic modification endowed UC-MSCs with prominent osteogenic differentiation potency and angiogenesis efficacy. More importantly, KL-EVs profoundly rescued multifaceted senescent phenotypes in both adult bone marrow mesenchymal stem cells (BMSCs) and human renal tubular epithelial cells (HK-2) in vitro. In particular, KL-EVs rescued the age-related differentiation bias of adult BMSCs by robustly prompting their osteogenic differentiation capacity. Taken together, we developed a novel type of UC-MSCs and isolated their EVs enriched with Klotho protein. This strategy integrated and enhanced the anti-aging effects of both entities in vitro, offering a new perspective for counteracting cellular senescence and alleviating age-associated degenerative alterations.<\/jats:p>","DOI":"10.3390\/ijms27188326","type":"journal-article","created":{"date-parts":[[2026,10,1]],"date-time":"2026-10-01T13:18:26Z","timestamp":1790860706000},"page":"8326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Characterization of Umbilical Cord Mesenchymal Stromal Cells Overexpressing Klotho and In Vitro Anti-Aging Efficacy of Their Derived Extracellular Vesicles"],"prefix":"10.3390","volume":"27","author":[{"given":"Anyuan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"methodology","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Shan","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"}]},{"given":"Bianlei","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Xiaorong","family":"Su","sequence":"additional","affiliation":[{"name":"Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"validation","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"given":"Wenying","family":"Deng","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2499-3604","authenticated-orcid":false,"given":"Hongxiang","family":"Wang","sequence":"additional","affiliation":[{"name":"Department of Hematology, The Central Hospital of Wuhan, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430014, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4900-7057","authenticated-orcid":false,"given":"Zhichao","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7884-0745","authenticated-orcid":false,"given":"Qiubai","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Rheumatology and Immunology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,19]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"258","DOI":"10.1186\/s13287-022-02927-8","article-title":"Human umbilical cord-derived mesenchymal stem cells not only ameliorate blood glucose but also protect vascular endothelium from diabetic damage through a paracrine mechanism mediated by MAPK\/ERK signaling","volume":"13","author":"Liu","year":"2022","journal-title":"Stem Cell Res. 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