Abstract 4292: Stem Cells for Myocardial Repair Using a Trans-Arterial Catheter
Using a pig model of postinfarction LV remodeling, this study examined marrow derived multi potent progenitors (MPC) 1 delivery after an infarct via a novel transarterial catheter (Microsyringe infusion catheter). Percutaneous transluminal angioplasty was performed in left anterior descending coronary artery to generate acute myocardial infarction (AMI, ischemia reperfusion with 60 minute no-flow ischemia). The trans-arterial catheter was then placed in the same coronary artery and either stem cells at 50 million MPC/ml (Cell, n=6) or saline (Control, n=6) was injected both with contrast to confirm delivery outside of vessel lumen. LV function was measured by MRI at time points of pre-AMI, week 1 and week 4 post AMI, whereas myocardial energy metabolism by 31P-MR spectroscopy at week 4. One week after the AMI, the ejection fraction was significantly reduced in both groups from baseline of ~ 50% to 31.3±3.9 (Cell) and 33.3±3.1 (Control). However, at week 4, the cell treated group had a significantly recovery of ejection fraction that was not observed in control group (Cell, 46.3+/−6.6; control, 35.4+/− 3.2 %, p<0.05). The functional improvements were accompanied by a significant higher myocardial bioenergetic efficiency (PCr/ATP: 2.03 ± 0.31 vs. 1.53 ± 0.28, Cell vs Control, p<0.05). Histological data demonstrated a significant stem cell engraftment in the entire LV. Some of the engrafted cells were co-staining positive for troponin T and/or N-cadherin suggesting differentiation to myogenic cells. In co-culture experiments, the progenitors significantly inhibited TNFa induced cytochrome C release from neonatal myocytes. In addition, the conditioned medium derived from stem cell culture inhibited hypoxia-induced HL-1 myocyte cell apoptosis. Further, under hypoxia culture condition these progenitors released significant more amount of VEGF (p<0.01). Thus, a paracrine associated anti-apoptosis effects may contribute significantly to the observed therapeutic effect of stem cell transplantation.