{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,20]],"date-time":"2026-02-20T18:33:30Z","timestamp":1771612410985,"version":"3.50.1"},"reference-count":72,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,3,14]],"date-time":"2022-03-14T00:00:00Z","timestamp":1647216000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004543","name":"China Scholarship Council","doi-asserted-by":"publisher","award":["201908080045"],"award-info":[{"award-number":["201908080045"]}],"id":[{"id":"10.13039\/501100004543","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Cells"],"abstract":"<jats:p>Induced pluripotent stem cell (iPSC) derived mesenchymal stem cells (iMSCs) represent a promising source of progenitor cells for approaches in the field of bone regeneration. Bone formation is a multi-step process in which osteogenesis and angiogenesis are both involved. Many reports show that the secretome of mesenchymal stromal stem cells (MSCs) influences the microenvironment upon injury, promoting cytoprotection, angiogenesis, and tissue repair of the damaged area. However, the effects of iPSC-derived MSCs secretome on angiogenesis have seldom been investigated. In the present study, the angiogenic properties of IFN-\u03b3 pre-conditioned iMSC secretomes were analyzed. We detected a higher expression of the pro-angiogenic genes and proteins of iMSCs and their secretome under IFN-\u03b3 and hypoxic stimulation (IFN-H). Tube formation and wound healing assays revealed a higher angiogenic potential of HUVECs in the presence of IFN-\u03b3 conditioned iMSC secretome. Sprouting assays demonstrated that within Coll\/HA scaffolds, HUVECs spheroids formed significantly more and longer sprouts in the presence of IFN-\u03b3 conditioned iMSC secretome. Through gene expression analyses, pro-angiogenic genes (FLT-1, KDR, MET, TIMP-1, HIF-1\u03b1, IL-8, and VCAM-1) in HUVECs showed a significant up-regulation and down-regulation of two anti-angiogenic genes (TIMP-4 and IGFBP-1) compared to the data obtained in the other groups. Our results demonstrate that the iMSC secretome, pre-conditioned under inflammatory and hypoxic conditions, induced the highest angiogenic properties of HUVECs. We conclude that pre-activated iMSCs enhance their efficacy and represent a suitable cell source for collagen\/hydroxyapatite with angiogenic properties.<\/jats:p>","DOI":"10.3390\/cells11060988","type":"journal-article","created":{"date-parts":[[2022,3,15]],"date-time":"2022-03-15T03:06:10Z","timestamp":1647313570000},"page":"988","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":34,"title":["Pre-Conditioning with IFN-\u03b3 and Hypoxia Enhances the Angiogenic Potential of iPSC-Derived MSC Secretome"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2825-9212","authenticated-orcid":false,"given":"Suya","family":"Wang","sequence":"first","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2040-7492","authenticated-orcid":false,"given":"Felix","family":"Umrath","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}]},{"given":"Wanjing","family":"Cen","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}]},{"given":"Ant\u00f3nio Jos\u00e9","family":"Salgado","sequence":"additional","affiliation":[{"name":"Life and Health Sciences Research Institute (ICVS), School of Medicine, University of Minho, Campus de Gualtar, 4710-057 Braga, Portugal"},{"name":"ICVS\/3B\u2019s\u2013PT Government Associate Laboratory, University of Minho, 4710-057 Braga, Portugal"}]},{"given":"Siegmar","family":"Reinert","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}]},{"given":"Dorothea","family":"Alexander","sequence":"additional","affiliation":[{"name":"Department of Oral and Maxillofacial Surgery, University Hospital T\u00fcbingen, 72076 T\u00fcbingen, Germany"}]}],"member":"1968","published-online":{"date-parts":[[2022,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/s41413-019-0069-4","article-title":"Human IPSC-Derived IMSCs Improve Bone Regeneration in Mini-Pigs","volume":"7","author":"Jungbluth","year":"2019","journal-title":"Bone Res."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1186\/s40729-017-0084-4","article-title":"Autogenous Bone Grafts in Oral Implantology-Is It Still a \u201cGold Standard\u201d? 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