Abstract 1844: Temporal engraftment and functional outcome of Bone Marrow Derived Multipotent Progenitor cell transplantation (MPC) in a porcine model of postinfarction Left Ventricular (LV) Remodeling
This study compares the short term and long term functional outcomes of bone marrow derived multipotent progenitor cells (MPC) transplantation. In the short term study, the LAD was occluded distal to the 2nd diagonal branch with PTCA balloon dilatation for 60 minutes (IR, 1 month follow-up) and MPC were delivered through a transarterial catheter, while in the long term study, the coronary artery was occluded with ligation (OCCL, 4 months follow-up). In both IR and OCCL cases, intra-myocardial injection of 50 million LacZ labeled MPC (Cell) was performed in the periscar region with 5 equal injections immediately after myocardial infarction, while in control animals (CONT) saline was injected. The myocardial bioenergetics (P-31 MRS) and LV function (MRI) were followed-up monthly (Table⇓). MPC transplantation resulted in improvement of ejection fraction in the OCCL study, which persists for 4 months. In the IR study, although the EF was not significantly different between the two groups at 7days postinfarction, Cell induced a significant improvement of EF at week 4 (Table⇓). The myocardial phosphorylation potential that is reflected by the PCr/ATP ratio was significantly higher in CELL treated group of both studies, which persists during high cardiac workstates secondary to catecholamine stimulation. Although the engraftment was low (less than 0.35%), a small portion of the engrafted cells were found co-staining positive for troponin T and/or N-cadherin suggesting differentiation to myogenic cells. The infarct size was similar between the groups at 10 days. However, the infarct size was significantly reduced at 4 months in the Cell group that was not observed in the CONT. These data demonstrate that MPC transplantation associated improvement in ventricular function and myocardial energetics persists for 4 months follow-up. The beneficial effects are likely caused by cell transplantation induced mobilization and differentiation of endogenous cardiac progenitors.
This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).