{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T15:08:51Z","timestamp":1784732931873,"version":"3.55.0"},"reference-count":169,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T00:00:00Z","timestamp":1781740800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Mol. Biosci."],"abstract":"<jats:p>Extracellular vesicles derived from mesenchymal stem cells (MSC-EVs) have biocompatibility and low immunogenicity. They can effectively mediate intercellular communication by transmitting various information molecules, including polypeptides, lipids, and nucleic acids, thereby demonstrating unique potential in the field of drug delivery. Given their crucial roles in immune regulation and regenerative medicine, an increasing number of studies are focusing on developing MSC-EVs as drug carriers. This paper presents a systematic review of the future development directions of MSC-EVs as drug carriers, with a particular emphasis on their origins and engineering modification or pretreatment strategies. By employing engineering techniques to modify MSC-EVs, it is possible to precisely regulate key properties such as drug-loading capacity and targeting ability, thereby providing a novel approach for efficient drug delivery. Meanwhile, this paper delves into the safety evaluation of MSC-EVs in clinical applications across different diseases, comprehensively assessing their safety and efficacy as drug carriers based on clinical studies in the fields of lungs, skin, nervous system, eyes, and gastrointestinal tract, among others. Furthermore, we provide an outlook on the potential value and challenges associated with the clinical application of MSC-EVs as drug carriers in various diseases in the future, aiming to offer theoretical support and research directions for promoting MSC-EVs as safe and effective drug carriers.<\/jats:p>","DOI":"10.3389\/fmolb.2026.1838554","type":"journal-article","created":{"date-parts":[[2026,6,18]],"date-time":"2026-06-18T04:41:22Z","timestamp":1781757682000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":1,"title":["Mesenchymal stem cells-derived extracellular vesicles as a novel drug delivery carrier: engineering strategies and clinical safety estimation"],"prefix":"10.3389","volume":"13","author":[{"given":"Na","family":"Liu","sequence":"first","affiliation":[{"name":"Center of Medical Research, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xue","family":"Zhao","sequence":"additional","affiliation":[{"name":"Department of Clinical Laboratory, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xicai","family":"Sun","sequence":"additional","affiliation":[{"name":"Department of Hospital Office, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongmei","family":"Liu","sequence":"additional","affiliation":[{"name":"Center of Medical Research, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Xu","sequence":"additional","affiliation":[{"name":"Department of Gynecology, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donghua","family":"Xu","sequence":"additional","affiliation":[{"name":"Center of Medical Research, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, Shandong, China"]},{"name":"Department of Rheumatology and Immunology, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenchang","family":"Sun","sequence":"additional","affiliation":[{"name":"Center of Medical Research, Weifang People\u2019s Hospital, Shandong Second Medical University","place":["Weifang, Shandong, China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,6,18]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"143","DOI":"10.12688\/f1000research.75580.1","article-title":"Effectiveness and safety profile of mesenchymal stem cell secretome as a treatment for severe cases of COVID-19: a randomized controlled trial","volume":"11","author":"Abdullah","year":"2022","journal-title":"F1000Research"},{"key":"B2","doi-asserted-by":"publisher","first-page":"264","DOI":"10.1186\/s13287-024-03868-0","article-title":"Safety and potential effects of intrathecal injection of allogeneic human umbilical cord mesenchymal stem cell-derived exosomes in complete subacute spinal cord injury: a first-in-human, single-arm, open-label, phase I clinical trial","volume":"15","author":"Akhlaghpasand","year":"2024","journal-title":"Stem Cell Res. and Ther."},{"key":"B3","doi-asserted-by":"publisher","first-page":"1348043","DOI":"10.3389\/fimmu.2024.1348043","article-title":"MSC exosomes attenuate sterile inflammation and necroptosis associated with TAK1-pJNK-NFKB mediated cardiomyopathy in diabetic ApoE KO mice","volume":"15","author":"Banerjee","year":"2024","journal-title":"Front. 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