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Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left ventricular remodeling and improve cardiac function after myocardial infarction

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Abstract

In the present study, we investigated whether mesenchymal stem cells (MSCs) overexpressing integrin-linked kinase (ILK) might regulate ventricular remodeling and cardiac function in a porcine myocardial infarction model. ILK-modified MSCs (ILK-MSCs) (n = 8), MSCs (n = 8) or placebo (n = 8) were injected into peri-infarct myocardium 7 days after ligation of the left anterior descending coronary artery. ILK expression was confirmed by immunofluorescence, real-time PCR, Western blot analysis, and flow cytometry. In vitro assays indicated increased proliferation and reduced apoptosis of MSCs due to overexpression of ILK. Echocardiographic, single-photon emission computed tomography and positron emission tomography analyses demonstrated preserved cardiac function and myocardial perfusion. Reduced fibrosis, increased cardiomyocyte proliferation, and enhanced angiogenesis were observed in the ILK-MSC group. Reduced apoptosis, as demonstrated by terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling analysis, was also noted. In conclusion, ILK promotes MSC proliferation and suppresses apoptosis. ILK-MSC transplantation improves ventricular remodeling and cardiac function in pigs after MI. It is associated with increased angiogenesis, reduced apoptosis, and increased cardiomyocyte proliferation. This may represent a new approach to the treatment of post-infarct remodeling and subsequent heart failure.

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Acknowledgments

We would like to thank Professor Zheng Xing of the University of Minnesota for expert technical assistance, and Congzhu Shi of the University of Pennsylvania for helpful comments and suggestions.

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Authors and Affiliations

  1. Department of Cardiology, The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Suzhou University, Changzhou, China

    Qing Mao

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

    Chengxi Lin, Jianshu Gao, Lina Kang & Biao Xu

  3. Department of Gerontology, The First People’s Hospital of Changzhou, The Third Affiliated Hospital of Suzhou University, Changzhou, China

    Xiulin Liang

  4. Department of Respiratory Medicine, Jinling Hospital, Nanjing University Medical School, Nanjing, China

    Wei Gao

  5. Department of Cardiothoracic Surgery, Jinling Hospital, Nanjing University Medical School, Nanjing, China

    Li Shen

Authors
  1. Qing Mao
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  2. Chengxi Lin
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  3. Jianshu Gao
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  4. Xiulin Liang
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  5. Wei Gao
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  6. Li Shen
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  7. Lina Kang
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  8. Biao Xu
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Corresponding author

Correspondence to Biao Xu.

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Qing Mao and Chengxi Lin have contributed equally to this article.

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Mao, Q., Lin, C., Gao, J. et al. Mesenchymal stem cells overexpressing integrin-linked kinase attenuate left ventricular remodeling and improve cardiac function after myocardial infarction. Mol Cell Biochem 397, 203–214 (2014). https://doi.org/10.1007/s11010-014-2188-y

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  • DOI: https://doi.org/10.1007/s11010-014-2188-y

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