{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:57:23Z","timestamp":1791925043248,"version":"4.3.4"},"reference-count":138,"publisher":"MDPI AG","issue":"4","license":[{"start":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T00:00:00Z","timestamp":1770595200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["21-74-30015-P"],"award-info":[{"award-number":["21-74-30015-P"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Recently, a growing number of scientific research and clinical studies have demonstrated the potential of extracellular vesicles (EVs) secreted by cells of different types for treating various diseases. It was shown that most frequently, substances and molecules excreted by the cells exert therapeutic or other effects, and not the cells themselves. Their cargo is wrapped in membrane envelopes, allowing it to survive for a longer time and find targets in organs and tissues as well as overcome various barriers, including the blood\u2013brain barrier. EVs from mesenchymal stromal (stem) cells (MSCs) have attracted particular interest, as MSCs possess immunomodulatory and tissue-repairing properties per se. However, their clinical use is severely limited due to the frequent lack of efficiency in clinical trials, as well as existing risks of tumorigenesis and pulmonary embolism. EVs isolated from MSCs may help circumvent these problems, but their composition and properties, like those of their progenitors, vary significantly between batches, owing to donor characteristics and cell culture conditions. EVs from immortalized MSCs offer greater potential for repeatability and uniformity but raise the question of whether cell immortalization products enter EVs and are transferred to target cells and\/or affect them. This review examines the most recent data on preconditioning techniques for MSC-derived EVs, EV characterization, large-scale manufacturing, storage, and the use of EVs from immortalized MSCs, including their characteristics and therapeutic properties, with a special emphasis on safety issues.<\/jats:p>","DOI":"10.3390\/ijms27041688","type":"journal-article","created":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T16:13:32Z","timestamp":1770653612000},"page":"1688","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":13,"title":["Characterization, Preconditioning, Safety, and Other Issues of MSC-Derived EVs and Secretome"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2757-9991","authenticated-orcid":false,"given":"Elena V.","family":"Alpeeva","sequence":"first","affiliation":[{"name":"Laboratory of Cell Biology, N.K. Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Vavilov Street 26, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anfisa S.","family":"Ryabchenko","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology, N.K. Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Vavilov Street 26, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5405-0212","authenticated-orcid":false,"given":"Ekaterina A.","family":"Vorotelyak","sequence":"additional","affiliation":[{"name":"Laboratory of Cell Biology, N.K. Koltzov Institute of Developmental Biology of Russian Academy of Sciences, Vavilov Street 26, 119334 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,2,9]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"4285215","DOI":"10.1155\/2016\/4285215","article-title":"Mesenchymal stromal cells and tissue-specific progenitor cells: Their role in tissue homeostasis","volume":"2016","author":"Klimczak","year":"2016","journal-title":"Stem Cells Int."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"143","DOI":"10.1126\/science.284.5411.143","article-title":"Multilineage potential of adult human mesenchymal stem cells","volume":"284","author":"Pittenger","year":"1999","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"741","DOI":"10.1007\/s12015-017-9759-8","article-title":"Eminent sources of adult mesenchymal stem cells and their therapeutic imminence","volume":"13","author":"Macrin","year":"2017","journal-title":"Stem Cell Rev. 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