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Stem Cells International
Volume 2017, Article ID 3794817, 11 pages
Research Article

Transplantation of Rat Mesenchymal Stem Cells Overexpressing Hypoxia-Inducible Factor 2α Improves Blood Perfusion and Arteriogenesis in a Rat Hindlimb Ischemia Model

1Department of Vascular Surgery, Zhongshan Hospital of Xiamen University, Xiamen, China
2Cancer Research Center, Medical College of Xiamen University, Xiamen, China
3Department of Cardiovascular Surgery, Xin Hua Hospital affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China
4Department of Vascular Surgery, Zhongshan Hospital of Fudan University, Shanghai, China

Correspondence should be addressed to Weifeng Lu; moc.361@mxfwul

Received 3 January 2017; Accepted 29 August 2017; Published 7 November 2017

Academic Editor: Boon C. Heng

Copyright © 2017 Weifeng Lu et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Mesenchymal stem cells (MSCs) have been increasingly tested in cell-based therapy to treat numerous diseases. Genetic modification to improve MSC behavior may enhance posttransplantation outcome. This study aims to test the potential therapeutic benefits of rat bone marrow MSCs overexpressing hypoxia-inducible factor 2α (rMSCsHIF-2α) in a rat hindlimb ischemia model. PBS, rMSCs, or rMSCsHIF-2α were injected into rat ischemic hindlimb. Compared with the injection of PBS or rMSCs, transplantation of rMSCsHIF-2α significantly improved blood perfusion, increased the number of vessel branches in the muscle of the ischemic hindlimb, and improved the foot mobility of the ischemic hindlimb (all ). rMSCHIF-2α transplantation also markedly increased the expression of proangiogenic factors VEGF, bFGF, and SDF1 and Notch signaling proteins including DII4, NICD, Hey1, and Hes1, whereas it reduced the expression of proapoptotic factor Bax in the muscle of the ischemic hindlimb. Overexpression of HIF-2α did not affect rMSC stemness and proliferation under normoxia but significantly increased rMSC migration and tube formation in matrigel under hypoxia (all ). RMSCsHIF-2α stimulated endothelial cell invasion under hypoxia significantly (). Genetic modification of rMSCs via overexpression of HIF-2α improves posttransplantation outcomes in a rat hindlimb ischemia model possibly by stimulating proangiogenic growth factors and cytokines.