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Injection of basic fibroblast growth factor together with adipose-derived stem cell transplantation: improved cardiac remodeling and function in myocardial infarction

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Abstract

Recent findings suggest that cell and gene transplantation in the infarcted myocardium may improve heart function. The aim of the study was to investigate the mechanism involved in improving heart function following the co-injection of adipose-derived stem cells (ADSCs) and basic fibroblast growth factor (bFGF) in a rat model of myocardial infarction. In this study, ADSCs were isolated from subcutaneous adipose tissues. The ADSCs were induced to differentiate into adipocytes, osteoblasts and cardiac myocytes in vitro. bFGF was co-injected with the ADSCs into the left ventricular wall in a rat myocardial infarction model. The structural and functional outcomes resulting from this transplantation were determined through detailed histological analysis and echocardiography. The graft size was significantly larger in the bFGF + ADSC group than in the PBS + ADSC group and PBS + bFGF group 4 weeks after injection (p < 0.05). The ADSCs were able to differentiate into cardiomyocytes, endothelial cells and vascular smooth muscle cells in vivo. There was a significant improvement in arteriole density within the infarcted area in the bFGF + ADSC group compared with the PBS + ADSC group and the PBS + bFGF group 4 weeks after transplantation (p < 0.05). The results of Western blot analysis showed that all of the treatments significantly reduced MMP2 and MMP9 protein levels compared with the PBS control group (p < 0.05) and that the levels of these proteins displayed the largest decrease in the bFGF + ADSC group (p < 0.05). In addition, the results of a quantitative analysis revealed that the proportion of fibrotic areas was significantly lower in the PBS + ADSC and bFGF + ADSC groups compared with the PBS-only group and PBS + bFGF group (p < 0.05). The combined application of bFGF and ADSC transplantation may significantly increase the number of arterioles, reduce the infarcted size, attenuate ventricular remodeling and improve cardiac function. This ADSC + bFGF treatment strategy (or a variation thereof) may prove to be broadly applicable to other candidate cell preparations used in regenerative medicine.

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Acknowledgments

This study was supported by the Technology Support Foundation for Xinjiang Uygur Autonomous Region of China (NO. 200891127), The National Natural Science young Foundation of China (NO. 81000089), The National Natural Science Foundation of China (NO. 81160026) and The National Natural Science Foundation of China (NO. 81060025). We present great thanks to BD. Chen for technical assistance in histological preparation and staining.

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    1. Department of Cardiology of the First Affiliated Hospital, Xinjiang Medical University, 1 Liyushan Rd, 830054, Ürūmqi, People’s Republic of China

      Baozhu Wang, Xiang Ma, Long Zhao, Xinrong Zhou, Yitong Ma, Huiping Sun, Yining Yang & Bangdang Chen

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    1. Baozhu Wang
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    Correspondence to Yitong Ma.

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    Baozhu Wang, Xiang Ma, Long Zhao and Xinrong Zhou have contributed equally to this work.

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    Wang, B., Ma, X., Zhao, L. et al. Injection of basic fibroblast growth factor together with adipose-derived stem cell transplantation: improved cardiac remodeling and function in myocardial infarction. Clin Exp Med 16, 539–550 (2016). https://doi.org/10.1007/s10238-015-0383-0

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