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Despite bone marrow (BM) being the most studied tissue source, cells with similar intrinsic properties can be isolated from adipose tissue (AT) and umbilical cord matrix (UCM). The present study aims to compare the angiogenic potential of MSC obtained from BM, AT and UCM that were genetically modified with vascular endothelial growth factor (VEGF)\u2010encoding minicircle (MC) vectors. The overexpression of VEGF combined with the intrinsic properties of MSC could represent a promising strategy towards angiogenic therapies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We established a microporation\u2010based protocol to transfect human MSC using VEGF\u2010encoding MC (MC\u2010VEGF). VEGF production levels were measured by an enzyme\u2010linked immunosorbent assay and a quantitative polymerase chain reaction. The<jats:italic>in vitro<\/jats:italic>angiogenic potential of transfected cells was quantified using cell tube formation and migration functional studies.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>MSC isolated from BM, AT or UCM showed similar levels of VEGF secretion after transfection with MC\u2010VEGF. Those values were significantly higher when compared to non\u2010transfected cells, indicating an effective enhancement of VEGF production. Transfected cells displayed higher<jats:italic>in vitro<\/jats:italic>angiogenic potential than non\u2010transfected controls, as demonstrated by functional<jats:italic>in vitro<\/jats:italic>assays. No significant differences were observed among cells from different sources.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Minicircles can be successfully used to transiently overexpress VEGF in human MSC, regardless of the cell tissue source, representing an important advantage in a clinical context (i.e., angiogenic therapy) because a standard protocol might be applied to MSC of different tissue sources, which can be differentially selected according to the application (e.g., autologous versus allogeneic settings).<\/jats:p><\/jats:sec>","DOI":"10.1002\/jgm.3342","type":"journal-article","created":{"date-parts":[[2021,4,19]],"date-time":"2021-04-19T05:43:51Z","timestamp":1618811031000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Minicircle\u2010based expression of vascular endothelial growth factor in mesenchymal stromal cells from diverse human tissues"],"prefix":"10.1002","volume":"23","author":[{"given":"Joana","family":"Serra","sequence":"first","affiliation":[{"name":"Department of Bioengineering and iBB \u2013 Institute for Bioengineering and Biosciences Instituto Superior T\u00e9cnico, Universidade de Lisboa Lisboa Portugal"}]},{"given":"Cl\u00e1udia P. A.","family":"Alves","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and iBB \u2013 Institute for Bioengineering and Biosciences Instituto Superior T\u00e9cnico, Universidade de Lisboa Lisboa Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2405-5845","authenticated-orcid":false,"given":"Joaquim M. S.","family":"Cabral","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and iBB \u2013 Institute for Bioengineering and Biosciences Instituto Superior T\u00e9cnico, Universidade de Lisboa Lisboa Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4840-6299","authenticated-orcid":false,"given":"Gabriel A.","family":"Monteiro","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and iBB \u2013 Institute for Bioengineering and Biosciences Instituto Superior T\u00e9cnico, Universidade de Lisboa Lisboa Portugal"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1091-7651","authenticated-orcid":false,"given":"Cl\u00e1udia L.","family":"da Silva","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and iBB \u2013 Institute for Bioengineering and Biosciences Instituto Superior T\u00e9cnico, Universidade de Lisboa Lisboa 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