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Combination of chemokine and angiogenic factor genes and mesenchymal stem cells could enhance angiogenesis and improve cardiac function after acute myocardial infarction in rats

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Abstract

Gene and stem-cell therapies hold promise for the treatment of ischemic cardiovascular disease. Combined stem cell, chemokine, and angiogenic growth factor gene therapy could augment angiogenesis, and better improve heart function in the infarcted myocardium. In order to prove this action, we established the animal model of myocardial infarction (MI) was by occlusion of the left anterior descending artery in rats. Seven days after surgery, 5.0 × 106 Ad-EGFP–MSC, 5.0 × 106 Ad-SDF-1–MSC, 5.0 × 106 Ad-VEGF–MSC, or 5.0 × 106 Ad-SDF–VEGF–MSC (Ad-SDF-1–VEGF–MSC) suspension in 0.2 ml of serum-free medium was injected into four sites in the infarcted hearts. Results showed that MSCs transfected with Ad-VEGF and Ad-SDF-1 produced more SDF-1 and VEGF protein than MSCs alone, the increased protein levels of VEGF and SDF-1 activated Akt in MSCs transfected with Ad-VEGF and Ad-SDF-1, and improved the survival capability of the MSCs in vitro and in vivo. These transplanted cells showed that the characteristic phenotype of cardiomyocyte (e.g., cTnt) and endothelial cells (e.g., CD31). Four weeks after transplantation, reduced infarct size and fibrosis, greater vascular density, and a thicker left ventricle wall were observed in Ad-SDF–VEGF–MSC group. Measurement of hemodynamic parameters showed an improvement in left ventricular performance in Ad-SDF–VEGF–MSC group compared with other groups. These results demonstrated that combination of chemokine and angiogenic factor gene and stem cells could enhance angiogenesis and improves cardiac function after acute myocardial infarction in rats.

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Abbreviations

MSCs:

Mesenchymal stem cells

VEGF:

Vascular endothelial growth factor

SDF-1α:

Stromal cell-derived factor-1 alpha

EGFP:

Enhanced green fluorescent protein

MI:

Myocardial infarction

Ad:

Adenoviral

LVSP:

Left ventricle systolic pressure

LVEDP:

Left ventricle end-diastolic pressure

+dP/dt max and −dP/dt max :

Rate of rise and fall of ventricular pressure

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Acknowledgments

We thank Professor Yongsheng Ren for his helpful instruction in heart function evaluation. We are grateful to Long Chen for help with immunofluorescence staining. We thank international science editing corporation for his helpful instruction in the article edition. This study was supported by grants from the National Natural Science Foundation of China (30700306), Hubei Natural Science Foundation (2005ABA079), Hubei Health Department Science Foundation (JX3B29), Hubei Education Department Science Foundation (Q200524003, B200624006), Yun Yang Medical College Science Foundation (2005QDJ01), and Shiyan Renmin Hospital Science Foundation, China.

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Authors and Affiliations

  1. Department of Cardiology, Institute of Clinical Medicine, Renmin Hospital, Yunyang Medical College, Shiyan, Hubei, 442000, People’s Republic of China

    Junming Tang, Jianing Wang, Fei Zheng, Xia Kong, Linyun Guo, Jianye Yang, Lei Zhang & Yongzhang Huang

  2. Department of Physiology, Yunyang Medical College, Shiyan, Hubei, 442000, People’s Republic of China

    Junming Tang

  3. Hubei Key Laboratory of Embryonic Stem Cell Research, Yunyang Medical College, Shi yan, Hubei, 442000, People’s Republic of China

    Junming Tang, Jianing Wang, Fei Zheng, Xia Kong, Linyun Guo, Jianye Yang, Lei Zhang & Yongzhang Huang

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  1. Junming Tang
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Correspondence to Junming Tang or Jianing Wang.

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Tang, J., Wang, J., Zheng, F. et al. Combination of chemokine and angiogenic factor genes and mesenchymal stem cells could enhance angiogenesis and improve cardiac function after acute myocardial infarction in rats. Mol Cell Biochem 339, 107–118 (2010). https://doi.org/10.1007/s11010-009-0374-0

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