European Journal of Heart Failure Advance Access originally published online on January 12, 2009
European Journal of Heart Failure 2009 11(3):238-245; doi:10.1093/eurjhf/hfn035
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Cell therapy generates a favourable chemokine gradient for stem cell recruitment into the infarcted heart in rabbits
1 Department of Internal Medicine, National Taiwan University Hospital, 7 Chung-Shan South Road, Taipei, Taiwan, Republic of China
2 Graduate Institute of Clinical Medicine, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
3 Department of Medical Imaging, National Taiwan University Hospital, Taipei, Taiwan, Republic of China
4 Department of Animal Science and Technology, National Taiwan University, Taipei, Taiwan, Republic of China
5 Department of Pharmacology, College of Medicine, National Taiwan University, Taipei, Taiwan, Republic of China
* Corresponding author. Tel: +886 2 2312 3456, Fax: +886 2 3322 3937, Email: mfchen{at}ntu.edu.tw
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Abstract |
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Aims: Stem cell recruitment into the heart is determined by a concentration gradient of stromal-derived factor 1 (SDF-1) from bone marrow to peripheral blood and from blood to injured myocardium. However, this gradient is decreased in chronic myocardial infarction (MI). This study evaluated the effect of cell therapy using bone marrow stromal cells (BMSCs) on an SDF-1 gradient in post-infarction rabbits.
Methods and results: Myocardial infarction was induced in male New Zealand white rabbits (2.5–3 kg) by ligation of the left anterior descending coronary artery. Two months later, the rabbits were randomized to either saline or BMSC (2 x 106 autologous BMSCs injected into the left ventricular cavity) treatment. Four weeks after therapy, the SDF-1 gradients from bone marrow to blood and from blood to myocardium increased in the BMSC group compared with the saline group. This was accompanied by an increase in cells positive for CD34, CD117, and STRO-1 in the myocardium, resulting in more capillary density, better cardiac function, and a decrease in infarct size.
Conclusion: Generation of an SDF-1 gradient towards the heart is a novel effect of BMSC-based cell therapy. This effect facilitates stem cell recruitment into remodelled myocardium and supports improvement in cardiac function.
Key Words: Stromal-derived factor 1 • Bone marrow stromal cell • Myocardial infarction • Ventricular remodelling
Received June 5, 2008; Revised October 13, 2008; Accepted November 24, 2008