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Hypoxia enhances the therapeutic potential of superparamagnetic iron oxide-labeled adipose-derived stem cells for myocardial infarction

  • Wang, Jian1, 2, 3
  • Xiang, Bo2, 4
  • Deng, Ji-xian2, 3
  • Lin, Hung-yu2
  • Freed, Darren H.2, 3, 5
  • Arora, Rakesh C.2, 3, 6
  • Tian, Gang-hong2, 3
  • 1 Huazhong University of Science and Technology, Department of Vascular Surgery, Union Hospital, Tongji Medical College, Wuhan, 430022, China , Wuhan (China)
  • 2 National Research Council of Canada, Winnipeg, R3B 1Y6, Canada , Winnipeg (Canada)
  • 3 University of Manitoba, Department of Physiology, Faculty of Medicine, Winnipeg, R3E 3P5, Canada , Winnipeg (Canada)
  • 4 University of Manitoba, Department of Pharmacology and Therapeutics, Faculty of Medicine, Winnipeg, R3E 0T6, Canada , Winnipeg (Canada)
  • 5 University of Alberta Hospital, Division of Cardiac Surgery, Edmonton, T6G 2B7, Canada , Edmonton (Canada)
  • 6 St. Boniface General Hospital, Cardiac Science Program, Institute of Cardiovascular Science, Winnipeg, R2H 2A6, Canada , Winnipeg (Canada)
Published Article
Journal of Huazhong University of Science and Technology [Medical Sciences]
Huazhong University of Science and Technology
Publication Date
Aug 08, 2017
DOI: 10.1007/s11596-017-1766-0
Springer Nature


Adipose-derived stem cells (ASCs) induce therapeutic angiogenesis due to pro-angiogenic cytokines secretion. Superparamagnetic iron oxide (SPIO) nanoparticles are critical for magnetic resonance (MR) tracking of implanted cells. Hypoxia is a powerful stimulus for angiogenic activity of ASCs. In this study, we investigated whether therapeutic potency could be enhanced by implantation of hypoxia-preconditioned SPIO-labeled ASCs (SPIOASCs) into the infarcted myocardium. ASCs and SPIOASCs were cultured under 2% O2 (hypoxia) or 95% air (normoxia). Cells were intramyocardially injected into the infarcted myocardium after 48-h culture. We found that hypoxia culture increased the mRNA expression of hypoxia-inducible factor-1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF) in ASCs and SPIOASCs. The VEGF protein in the conditioned medium was significantly higher in hypoxic ASCs and SPIOASCs than in normoxic ASCs and SPIOASCs. The capillary density and left ventricular contractile function in the infarcted myocardium were significantly higher 4 weeks after implantation with hypoxic ASCs and SPIOASCs than with normoxic ASCs and SPIOASCs. Improvement in the capillary density and left ventricle function didn’t differ between hypoxic ASCs-transplanted rats and hypoxic SPIOASCs-transplanted rats. Hypoxic culture enhanced the angiogenic efficiency of ASCs. It was concluded that implantation of hypoxic ASCs or SPIOASCs promotes therapeutic angiogenesis and cardiac function recovery in the infarcted myocardium. SPIO labeling does not impact the beneficial effect of hypoxic ASCs.

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