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

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 monomiclear cells (N4NCs, 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 ischaernic 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 orsaline. Capillary density (1132 +/- 69 versus 903 +/- 44 per mm(2), 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 angiopoictin-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 ischaernic 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. (c) 2007 European Society of Cardiology. Published by Elsevier B.V. All rights reserved.