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

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 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 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. © 2007 European Society of Cardiology.