Multipotent Cardiovascular Progenitor Regeneration of the Myocardium after MI

Myocardial infarction (MI) and other forms of ischemic heart disease accounts for 60% of HF, which is the largest cause of human mortality (13% of all mortality). The major biological problem that underlies the disease is that a large number of heart muscle cells are killed or damaged by ischemic injury, and the adult heart has only negligible capacity to replace these cells. Consequently, cell therapy emerged as a promising strategy to reconstitute the myocardium.

This project tested the hypothesis that multipotent cardiac progenitors (MCPs) could contribute to new cardiac muscle after intracoronary infusion into the heart after MI. MCPs resemble normal cardiac progenitors that give rise to the fetal heart during embryogenesis. In vitro data had shown robust differentiation into cardiac muscle and endothelial cells. Cell production, cell labelling with a stable 19F fluorine reagent to track the cells, and cell delivery via intracoronary catheterization in swine were optimized resulting in a protocol that is compatible with current reperfusion strategies used clinically and resulted in 4-9% cell retention 1 hr after the procedure. 9 procedures were completed to gauge efficacy and safety (4 no cell control and 5 infusions of 250 million MCPs each). 2 out of 5 cell-infused pigs died after treatment. No cardiac events were observed in the no cells infusions. Of the 3 remaining cell infused pigs, all showed an improvement in cardiac function assessed by functional MRI between 14 and 30 days after MI that was not seen in the no cells-infused pigs. However, 19F MRI showed no cell retention at 30 days post-MI. Thus, we conclude 1) the MCPs provided a therapeutic effect, 2) the effect was most likely due to paracrine signaling from the infused cells, and 3) the cell infusion as performed carried a high risk of adverse cardiac events.