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

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Summary

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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Authors and Affiliations

  1. Department of Vascular Surgery, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430022, China

    Jian Wang  (王 剑)

  2. National Research Council of Canada, Winnipeg, R3B 1Y6, Canada

    Jian Wang  (王 剑), Bo Xiang  (向 波), Ji-xian Deng  (邓继先), Hung-yu Lin  (林宏宇), Darren H. Freed, Rakesh C. Arora & Gang-hong Tian  (田钢虹)

  3. Department of Physiology, Faculty of Medicine, University of Manitoba, Winnipeg, R3E 3P5, Canada

    Jian Wang  (王 剑), Ji-xian Deng  (邓继先), Darren H. Freed, Rakesh C. Arora & Gang-hong Tian  (田钢虹)

  4. Department of Pharmacology and Therapeutics, Faculty of Medicine, University of Manitoba, Winnipeg, R3E 0T6, Canada

    Bo Xiang  (向 波)

  5. Division of Cardiac Surgery, University of Alberta Hospital, Edmonton, T6G 2B7, Canada

    Darren H. Freed

  6. Cardiac Science Program, Institute of Cardiovascular Science, St. Boniface General Hospital, Winnipeg, R2H 2A6, Canada

    Rakesh C. Arora

Authors
  1. Jian Wang  (王 剑)
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  2. Bo Xiang  (向 波)
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  3. Ji-xian Deng  (邓继先)
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  4. Hung-yu Lin  (林宏宇)
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  5. Darren H. Freed
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  6. Rakesh C. Arora
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  7. Gang-hong Tian  (田钢虹)
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Corresponding authors

Correspondence to Jian Wang  (王 剑) or Gang-hong Tian  (田钢虹).

Additional information

This work was supported by the National Natural Science Foundation of China (No. 81200105), the Scientific Research Foundation of Wuhan Union Hospital (No. 02.03.2017-34), the Natural Science Foundation of Hubei Province of China (No. 2015CFB457), the China Postdoctoral Science Foundation (No. 20100470050), Canadian Institute of Health Research (CIHR) (No. 200806RMF-189873-RMC-CDAA-42533), and National Research Council of Canada (NRC).

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Wang, J., Xiang, B., Deng, Jx. et al. Hypoxia enhances the therapeutic potential of superparamagnetic iron oxide-labeled adipose-derived stem cells for myocardial infarction. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 37, 516–522 (2017). https://doi.org/10.1007/s11596-017-1766-0

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  • DOI: https://doi.org/10.1007/s11596-017-1766-0

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