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European Journal of Heart Failure 2007 9(8):747-753; doi:10.1016/j.ejheart.2007.03.008
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© 2007 European Society of Cardiology

Paracrine effects of direct intramyocardial implantation of bone marrow derived cells to enhance neovascularization in chronic ischaemic myocardium

Hung-Fat Tsea,*, Chung-Wah Siua, Shu-Guang Zhua, Liao Songyana, Qing-Yong Zhanga, Wing-Hon Laia, Yok-Lam Kwongb, John Nichollsc and Chu-Pak Laua

a Division of Cardiology, The University of Hong Kong, Queen Mary Hospital Hong Kong, China
b Division of Hematology, The University of Hong Kong, Queen Mary Hospital Hong Kong, China
c Department of Pathology, The University of Hong Kong, Queen Mary Hospital Hong Kong, China

* Corresponding author. Cardiology Division, Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China. Tel.: +852 2855 3598; fax: +852 2818 6304. E-mail address: hftse{at}hkucc.hku.hk


  Abstract

Objective: To determine the optimal bone marrow (BM) cell types, and their potential mechanisms of action for neovascularization in chronic ischaemic myocardium.

Methods and results: The functional effects, angiogenic potential and cytokine expression of direct intramyocardial implantation of autologous BM CD31-positive endothelial progenitor cells (EPC, n=9), BM mononuclear cells (MNCs, n=9), and saline (n=9) were compared in a swine model of chronic ischaemic myocardium. Autologous BM cells were harvested and catheter-based electromechanical mapping-guided direct intramyocardial injection was performed to target ischaemic myocardium. After 12 weeks, injection of BM-MNC resulted in significant improvements in left ventricular dP/dt (+21±8%, P=0.032), left ventricular pressure (+17±4%, P=0.048) and regional microsphere myocardial perfusion over ischaemic endocardium (+74±28%, P<0.05) and epicardium (+73±29%, P<0.05). No significant effects were observed following injection of BM-EPC or saline. Capillary density (1132±69 versus 903±44 per mm2, P=0.047) and expression of mRNA of vascular endothelial growth factor (VEGF, 32.3±5.6 versus 13.1±3.7, P<0.05,) and angiopoietin-2 (23.9±3.6 versus 13.7±3.1, P<0.05) in ischaemic myocardium was significantly greater in the BM-MNC group than the saline group. The capillary density in ischaemic myocardium demonstrated a significant positive correlation with VEGF expression (r=0.61, P<0.001).

Conclusion: Catheter-based direct intramyocardial injection of BM-MNC enhanced angiogenesis more effectively than BM-EPC or saline, possibly via a paracrine effect, with increased expression of VEGF that subsequently improved cardiac performance of ischaemic myocardium.

Key Words: Bone marrow • Ischaemic myocardium • Neovascularization

Received October 31, 2006; Revised February 24, 2007; Accepted March 19, 2007


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