{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T11:09:18Z","timestamp":1788865758453,"version":"build-2803163510"},"reference-count":29,"publisher":"OAE Publishing Inc.","issue":"3","content-domain":{"domain":["oaepublish.com"],"crossmark-restriction":false},"short-container-title":["Extracell Vesicles Circ Nucleic Acids."],"abstract":"<jats:p>Aim: We investigated whether the secretome, particularly small extracellular vesicles (sEVs), obtained from deferoxamine (DFO)-pretreated stem cells from human exfoliated deciduous teeth (SHED), could promote angiogenesis in human umbilical vein endothelial cells (HUVECs) and support vascularized tissue integration under preliminary ectopic implantation conditions.<\/jats:p>\n                  <jats:p>Methods: SHED were treated with DFO (2.5, 5, 10 \u03bcM), and RNA sequencing was performed to analyze gene expression changes in DFO-treated SHED. The effects of the DFO-pretreated SHED secretome and the isolated sEVs (DFO-sEVs) on HUVEC migration were evaluated. The angiogenic capacity was assessed using wound healing, Transwell migration, and tube formation assays. DFO-sEVs were also tested for their ability to regulate macrophage polarization using immunofluorescence staining. Finally, DFO-sEVs were encapsulated in hydrogels and subcutaneously implanted into Sprague-Dawley rats, and their pro-angiogenic capacity in vivo was assessed via histological staining.<\/jats:p>\n                  <jats:p>Results: RNA-seq analysis indicated that DFO pretreatment modulated SHED pathways related to hypoxia response, cell adhesion, and inflammation. The secretome from SHED pretreated with 5 \u03bcM DFO significantly promoted HUVEC migration and tube formation. DFO-sEVs, particularly from the 5 \u03bcM DFO group, demonstrated superior pro-angiogenic effects compared to sEVs from untreated SHED both in vitro and in vivo. Furthermore, DFO-sEVs drove macrophages to adopt an M2-like reparative polarization.<\/jats:p>\n                  <jats:p>Conclusion: DFO pretreatment functionally potentiates the pro-angiogenic and immunomodulatory properties of SHED-derived sEVs. The findings suggest that DFO-sEVs may provide a bioactive component for promoting angiogenesis and facilitating tissue integration.<\/jats:p>","DOI":"10.20517\/evcna.2026.48","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T10:30:56Z","timestamp":1788863456000},"page":"1428-44","update-policy":"https:\/\/doi.org\/10.20517\/oae.crossmark.policy","source":"Crossref","is-referenced-by-count":0,"title":["Small extracellular vesicles from deferoxamine-primed stem cells promote angiogenesis and tissue 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