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Vascular endothelial growth factor (VEGF) is released from MSCs as a paracrine trophic factor and contributes to the therapeutic effects of the stem cell by regulating angiogenesis and promoting revascularization in injured tissues. Interleukin\u20108 (IL\u20108), an inflammatory chemokine with potent proangiogenic properties, is upregulated in the ischemic brain and has been shown to promote homing of bone marrow\u2010derived cells to injured sites. However, the effect of IL\u20108 on MSCs paracrine function remains unknown. We found that IL\u20108 induced VEGF production and phosphorylation of Akt and ERK. Both effects could be blocked by inhibitors (LY294002, PD098059) or siRNA\u2010mediated silencing of Akt and ERK in human bone marrow MSCs (hBM\u2010MSCs). IL\u20108\u2010induced VEGF production in hBM\u2010MSCs significantly increased tube formation on Matrigel compared with basal secreted VEGF. In a rat stroke model, administration of IL\u20108\u2010treated hBM\u2010MSCs decreased the infarction volume and increased angiogenesis in the ischemic boundary zone compared with hBM\u2010MSC treatment alone. In conclusion, IL\u20108 stimulates VEGF production in hBM\u2010MSCs in part via the PI3K\/Akt and MAPK\/ERK signal transduction pathways and that administration of IL\u20108\u2010treated hBM\u2010MSCs increases angiogenesis after stroke. This approach may be used to optimize MSC\u2010based therapies for numerous diseases including stroke, myocardial ischemia, and spinal cord injury.<\/jats:p><\/jats:sec>","DOI":"10.1002\/cbin.10294","type":"journal-article","created":{"date-parts":[[2014,5,5]],"date-time":"2014-05-05T11:40:47Z","timestamp":1399290047000},"page":"1050-1059","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":107,"title":["IL\u20108 enhances the angiogenic potential of human bone marrow mesenchymal stem cells by increasing vascular endothelial growth factor"],"prefix":"10.1002","volume":"38","author":[{"given":"Yun","family":"Hou","sequence":"first","affiliation":[{"name":"Department of Biomedical Science College of Medicine Catholic University of Korea 505 Banpo\u2010dong, Socho\u2010gu Seoul 137\u2010701 Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chung 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