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Herein, we examined the angiogenic potential of EVs derived from genetically modified mesenchymal stromal cells (MSCs), focusing on the angio-micro RNAs (miRNAs) in EVs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Methods:<\/jats:title>\n            <jats:p>Bone marrow-derived MSCs (BM-MSCs) were transfected with lentiviral vectors containing specific angio-miRNAs (miRNA-126, -135b, or -210), and miRNA overexpression was confirmed using quantitative polymerase chain reaction (qPCR). EVs were isolated from the BM-MSC culture medium and characterised using fluorometry, nanoparticle tracking analysis, and ExoScreen assays. <jats:italic>In vitro,<\/jats:italic> human umbilical vein endothelial cells (HUVECs) were used to evaluate the angiogenic potential of the EVs. <jats:italic>In vivo<\/jats:italic>, EVs were injected into the ischaemic hindlimb muscles of mice, and limb ischaemia severity, blood perfusion, and histological analysis of muscle tissue were performed.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Results:<\/jats:title>\n            <jats:p>qPCR analysis confirmed the overexpression of angio-miRNAs in MSCs transfected with lentiviral vectors. Isolated EVs expressed CD63 and had consistent protein-to-particle ratios. Tube formation was significantly enhanced when HUVECs were cultured with EV126, EV135b, or their combination (EV126\u2009+\u2009EV135b) (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05), compared to BM-MSC co-culture. <jats:italic>In vivo<\/jats:italic>, only the double and triple EV groups significantly improved limb perfusion compared to the EVcontrol (<jats:italic>p<\/jats:italic>\u2009&lt;\u20090.05); single EVs showed no significant difference. Histological analysis showed increased capillary density in ischaemic muscles following injection of combined EVs.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusion:<\/jats:title>\n            <jats:p>EVs derived from genetically modified MSCs promoted angiogenesis both <jats:italic>in vitro<\/jats:italic> and <jats:italic>in vivo<\/jats:italic>, with a combination of modified EVs demonstrating significantly superior therapeutic effects than single or native EVs.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1007\/s13770-025-00741-w","type":"journal-article","created":{"date-parts":[[2025,7,31]],"date-time":"2025-07-31T05:21:13Z","timestamp":1753939273000},"page":"993-1003","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Angiogenic Ability of Extracellular Vesicles Derived from Angio-miRNA-Modified Mesenchymal Stromal Cells"],"prefix":"10.1007","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0009-0003-1250-5348","authenticated-orcid":false,"given":"Yoshiki","family":"Wada","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3444-8842","authenticated-orcid":false,"given":"Toshifumi","family":"Kudo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anri","family":"Koyanagi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomomi","family":"Kusakabe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ayako","family":"Inoue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yusuke","family":"Yoshioka","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0776-9918","authenticated-orcid":false,"given":"Takahiro","family":"Ochiya","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5206-2842","authenticated-orcid":false,"given":"Shoji","family":"Fukuda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,31]]},"reference":[{"key":"741_CR1","doi-asserted-by":"publisher","first-page":"1642","DOI":"10.1016\/j.jvs.2015.07.065","volume":"62","author":"AM Abu Dabrh","year":"2015","unstructured":"Abu Dabrh AM, Steffen MW, Undavalli C, Asi N, Wang Z, Elamin MB, et al. 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