Abstract 1046: Paracrine Effects of Direct Intramyocardial Implantation of Bone Marrow Mononuclear Cells for Enhancement of Neovascularization in Chronic Ischemic Myocardium
Background: Prior studies suggested that direct intramyocardial injection of bone marrow (BM) induced angiogenesis in chronic ischemic myocardium. BM endothelial progenitor cell (EPC) has been postulated to play an important role in inducing angiogenesis. However, the optimal BM cell types and mechanism of action for angiogenesis remain unclear.
Methods: We compared the functional effects of direct intramycoardial implantation of 1x107 cells/ml autologous BM CD31 + EPCs, n=9) or BM MNCs (n=9), versus saline (n=9) in a swine model chronically ischemic myocardium. Catheter based direct intramyocardial injection was performed at ischemic left circumflex artery (LCX) territory as guided by electromechanical mapping. The left anterior descending artery territory was acted as control. Microsphere myocardial perfusion, global cardiac perfromance (+dP/dt), capillary density and vascular endothelial growth factor (VEGF) expression were measured before and at 3 months after procedure.
Results: A mean of 14±6 injections (0.1ml each) were performed in each animal. Direct intramyocardial injection of BM MNC, but not CD31+EPC resulted in significant increase expression of VEGF (Fig 1⇓), myocardial capillary density (Fig 2⇓) and microsphere myocardial perfusion (Fig 3⇓) at ischemic LCX territory as comapred with saline. Furthemore, +dP/dt was only significant improved in BM MNC treated animals after procedure (Fig 4⇓).
Conclusions: Direct intramycoardial injection of BM MNC was more effective than EPC alone in enhancement of angiogenesis via paracrine effect with increase expression of VEGF, and resulted in improvement in cardiac performance in ischemic myocardium.