Transmyocardial drilling revascularization combined with heparinized bFGF-incorporating stent activates resident cardiac stem cells via SDF-1/CXCR4 axis
- Department of Cardiac Surgery and Neurology, The First Hospital of China Medical University, Shenyang 110001 (China)
- College of Life Science, Nankai University, Tianjin 300036 (China)
- Department of Medical Genetics, China Medical University, Shenyang 110001 (China)
- Institute of Biomedical Engineering, Peking Union Medical College, Beijing 100730 (China)
Objective: To investigate whether transmyocardial drilling revascularization combined with heparinized basic fibroblast growth factor (bFGF)-incorporating degradable stent implantation (TMDRSI) can promote myocardial regeneration after acute myocardial infarction (AMI). Methods: A model of AMI was generated by ligating the mid-third of left anterior descending artery (LAD) of miniswine. After 6 h, the animals were divided into none-treatment (control) group (n = 6) and TMDRSI group (n = 6). For TMDRSI group, two channels with 3.5 mm in diameter were established by a self-made drill in the AMI region, into which a stent was implanted. Expression of stromal cell-derived factor-1{sub {alpha}} (SDF-1{sub {alpha}}) and CXC chemokine receptor 4 (CXCR4), cardiac stem cell (CSC)-mediated myocardial regeneration, myocardial apoptosis, myocardial viability, and cardiac function were assessed at various time-points. Results: Six weeks after the operation, CSCs were found to have differentiated into cardiomyocytes to repair the infarcted myocardium, and all above indices showed much improvement in the TMDRSI group compared with the control group (P < 0.001). Conclusions: The new method has shown to be capable of promoting CSCs proliferation and differentiation into cardiomyocytes through activating the SDF-1/CXCR4 axis, while inhibiting myocardial apoptosis, thereby enhancing myocardial regeneration following AMI and improving cardiac function. This may provide a new strategy for myocardial regeneration following AMI. -- Highlights: Black-Right-Pointing-Pointer The effects of TMDR and bFGF-stent on myocardial regeneration were studied in a pig model of AMI. Black-Right-Pointing-Pointer TMDR and bFGF-stent implantation activated CSCs via the SDF-1/CXCR4 axis. Black-Right-Pointing-Pointer CSC-mediated myocardial regeneration improved cardiac function. Black-Right-Pointing-Pointer It may be a new therapeutic strategy for AMI.
- OSTI ID:
- 22212301
- Journal Information:
- Experimental Cell Research, Vol. 318, Issue 4; Other Information: Copyright (c) 2011 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); ISSN 0014-4827
- Country of Publication:
- United States
- Language:
- English
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