https://scholars.lib.ntu.edu.tw/handle/123456789/545688
標題: | Mesenchymal stem cell-based HSP70 promoter-driven VEGFA induction by resveratrol promotes angiogenesis in a mouse model | 作者: | Chen Y.-B. Lan Y.-W. Hung T.-H. Chen L.-G. Choo K.-B. Cheng W.T.K. Lee, Hsuan-Shu Chong K.-Y. |
關鍵字: | Angiogenesis; Hsp70 promoter; Mouse model; Resveratrol; Stem cell-based gene therapy; VEGFA | 公開日期: | 2015 | 出版社: | Cell Stress and Chaperones | 卷: | 20 | 期: | 4 | 起(迄)頁: | 643-652 | 來源出版物: | Cell Stress and Chaperones | 摘要: | Several studies of stem cell-based gene therapy have indicated that long-lasting regeneration following vessel ischemia may be stimulated through VEGFA gene therapy and/or MSC transplantation for reduction of ischemic injury in limb ischemia and heart failure. The therapeutic potential of MSC transplantation can be further improved by genetically modifying MSCs with genes which enhance angiogenesis following ischemic injury. In the present study, we aimed to develop an approach in MSC-based therapy for repair and mitigation of ischemic injury and regeneration of damaged tissues in ischemic disease. HSP70 promoter-driven VEGFA expression was induced by resveratrol (RSV) in MSCs, and in combination with known RSV biological functions, the protective effects of our approach were investigated by using ex vivo aortic ring coculture system and a 3D scaffolds in vivo model. Results of this investigation demonstrated that HSP promoter-driven VEGFA expression in MSC increased approximately 2-fold over the background VEGFA levels upon HSP70 promoter induction by RSV. Exposure of HUVEC cells to medium containing MSC in which VEGFA had been induced by cis-RSV enhanced tube formation in the treated HUVEC cells. RSV-treated MSC cells differentiated into endothelial-like phenotypes, exhibiting markedly elevated expression of endothelial cell markers. These MSCs also induced aortic ring sprouting, characteristic of neovascular formation from pre-existing vessels, and additionally promoted neovascularization at the MSC transplantation site in a mouse model. These observations support a hypothesis that VEGFA expression induced by cis-RSV acting on the HSP70 promoter in transplanted MSC augments the angiogenic effects of stem cell gene therapy. The use of an inducible system also vastly reduces possible clinical risks associated with constitutive VEGFA expression. ? 2015, Cell Stress Society International. |
URI: | https://www.scopus.com/inward/record.uri?eid=2-s2.0-84930865264&doi=10.1007%2fs12192-015-0588-x&partnerID=40&md5=349548905f2e57ed4af9c5fea3154f75 https://scholars.lib.ntu.edu.tw/handle/123456789/545688 |
ISSN: | 1355-8145 | DOI: | 10.1007/s12192-015-0588-x | SDG/關鍵字: | cell marker; heat shock protein 70; resveratrol; unclassified drug; VEGFA protein; heat shock protein 70; resveratrol; stilbene derivative; vasculotropin A; angiogenesis; animal cell; Article; biological functions; cell differentiation; cell proliferation; cell regeneration; coculture; controlled study; cytotoxicity; ex vivo study; female; heart protection; human; human cell; in vivo study; ischemia; male; mesenchymal stem cell transplantation; mouse; neovascularization (pathology); nonhuman; phenotype; priority journal; protein expression; stem cell gene therapy; tissue injury; umbilical vein endothelial cell; vascular ring; angiogenesis; animal; aorta; bone marrow cell; C57BL mouse; cell culture; cell culture technique; cell survival; cytology; disease model; drug effects; genetics; in vitro study; ischemia; isomerism; mesenchymal stem cell transplantation; mesenchymal stroma cell; metabolism; pathology; Rice stripe virus; Animals; Aorta; Bone Marrow Cells; Cell Culture Techniques; Cell Differentiation; Cell Proliferation; Cell Survival; Cells, Cultured; Coculture Techniques; Disease Models, Animal; HSP70 Heat-Shock Proteins; Human Umbilical Vein Endothelial Cells; Humans; In Vitro Techniques; Ischemia; Isomerism; Mesenchymal Stem Cell Transplantation; Mesenchymal Stromal Cells; Mice; Mice, Inbred C57BL; Neovascularization, Physiologic; Stilbenes; Vascular Endothelial Growth Factor A |
顯示於: | 醫學系 |
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