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Intravenously delivered mesenchymal stem cells prevent microvascular obstruction formation after myocardial ischemia/reperfusion injury

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Abstract

Microvascular obstruction (MVO) after primary percutaneous coronary intervention (pPCI) is identified as an independent risk factor for poor prognosis in patients with acute myocardial infarction (AMI). The inflammatory response induced by ischemia and reperfusion (I/R) injury is considered one of the main mechanisms of MVO. Mesenchymal stem cells (MSCs) are a unique stromal cell type that confers an immunomodulatory effect in cardiac disease. The present study aimed to investigate whether immediate intravenous delivery of MSCs could be used as a potential therapeutic method to attenuate MVO formation. A cardiac catheterization-induced porcine model of myocardial I/R injury was established, and allograft MSCs were immediately delivered intravenously. Cardiac magnetic resonance (CMR) imaging was performed on days 2 and 7 after the operation to determine the infarct area, MVO, and cardiac function. The pigs with allograft MSCs showed decreased MVO and infarct size, as well as an improved left ventricular ejection fraction (LVEF). Histological analysis revealed decreased myocyte area, fibrosis, and inflammatory cell infiltration in the peri-infarct zone of pigs with allograft MSCs. Moreover, the concentrations of interleukin-1β (IL-1β), interleukin-6 (IL-6) and C-reactive protein (CRP) in the serum were reduced in the allograft MSC group compared to the control group. Flow cytometry indicated decreased natural killer (NK) cells in the peripheral blood and ischemic heart tissue in the pigs with allograft MSCs. In summary, allograft MSCs delivered intravenously and immediately after myocardial I/R injury can attenuate MVO formation in a porcine model through a decline in the number of NK cells in the myocardium.

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Acknowledgements

This work was supported by grants from the Natural Science Foundation of China (81870358), the Funds for Jiangsu Provincial Key Medical Discipline (ZDXKB2016013), the Key Projects of Science and Technology of Jiangsu Province (BE2016607 and BE2019602), the Funds for Jiangsu Provincial Medical Youth Talent (QNRC2016033), and the Programs of the Science Foundation in Nanjing (ZKX17011 and YKK17095).

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  1. Junzhuo Wang and Ziwei Chen equally contributed to this article.

Authors and Affiliations

  1. Department of Cardiology, Drum Tower Hospital, State Key Laboratory of Pharmaceutical Biotechnology, Medical School of Nanjing University, No. 321 Zhongshan Road, Nanjing, 210008, China

    Junzhuo Wang, Jinxuan Zhao, Jiaxin Hu, Xuan Sun, Jun Xie & Biao Xu

  2. Department of Cardiology, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, China

    Ziwei Chen, Qing Dai, Zilun Wei & Biao Xu

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  1. Junzhuo Wang
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Wang, J., Chen, Z., Dai, Q. et al. Intravenously delivered mesenchymal stem cells prevent microvascular obstruction formation after myocardial ischemia/reperfusion injury. Basic Res Cardiol 115, 40 (2020). https://doi.org/10.1007/s00395-020-0800-8

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