Direct Injection of Allogeneic Multipotent Adult Progenitor Cells Improves Cardiac Function after Myocardial Infarct.

Multipotent adult progenitor cells (MAPC) are an early stem cell population identified in the bone marrow of adults. They have been shown to be capable of differentiating into cell populations derived from all 3 germ layers. We hypothesized that delivery of MAPC in the peri-infarct period could lead to improved cardiac function. MAPC were isolated from the bone marrow of Sprague-Dawley rats and stably labeled by using a lentiviral construct encoding green fluorescent protein (GFP). In-vitro differentiation assays confirmed that the GFP-tagged MAPCs had retained the potential for tri-lineage differentiation. Myocardial infarction was induced in Lewis rats by direct LAD ligation. Lewis rats received Sprague-Dawley MAPC either immediately after LAD ligation by directly injecting into the infarct border zone (5 injections of 400,000 cells per injection) or 24 h after MI by intravenous infusion (2 million cells). Immunohistochemistry was performed to identify MAPC (GFP positive cells) within the infarct zone 2 weeks after MI. We identified MAPC in the infarct border zone of all animals that received direct injection of MAPC, 2 weeks after MI, but did not identify any MAPC following intravenous infusion. Echocardiography was performed to determine if the delivery of MAPC to the myocardium at the time of MI led to improvement in cardiac function. At 2 weeks post-MI, we observed a significant increase in shortening fraction in those animals that received direct injection of MAPC compared to control (13.9 ± 2.2% (n=4) vs. 24.0 ± 6.6% (n=7), p=0.018). These data demonstrate that MAPC delivery to acutely infracted myocardium may offer significant benefit. These data further suggest that MAPC are capable of surviving in the myocardial tissue even when used in an allogeneic strategy without inducing a significant increase in inflammation or rejection.