Abstract 3898: Human Cardiomyocyte Progenitor Cells Regenerate Infarcted Myocardium and Preserve Long-Term Cardiac Function in Mice
Introduction: Recently, we identified a cardiomyocyte progenitor cell (CMPC) population in the human fetal and adult heart. In vitro, CMPCs differentiate into beating cardiomyocytes, as well as endothelial cells and smooth muscle cells. In this study, we compared the regenerative capacity of undifferentiated CMPCs and CMPC-derived cardiomyocytes (CMPC-CM) after transplantation into ischemic myocardium in a long-term follow-up experiment.
Material and Methods: Isolated CMPCs were differentiated into CMPC-CM in vitro. After induction of myocardial infarction (MI) in SCID mice, a total of 0.5x106 CMPCs (n=10), CMPC-CM (n=10) or 10 μl PBS (n=9) was injected into two sites in the infarct borderzone. Cardiac function was measured 2 days, 4 weeks, and 12 weeks after MI by 9.4T MRI.
Results: Cell-injection led to a higher ejection fraction at all timepoints compared to vehicle and reduced the extent of left ventricular (LV) remodeling, indicated by the lower end-diastolic volume 12 weeks post-MI (149±13μl (CMPC) and 180±19μl (CMPC-CM)) versus vehicle (279±20μl, p<0.01). The same effect was observed for the end-systolic volume. These effects were not due differences in infarct size, which was similar between groups 2 days post-MI. Interestingly, the transplantation of CMPCs, prevented progression of wall-thinning in the infarcted area up to 12 weeks post-MI (638±45μm in CMPCs vs. 429±41μm in controls, p<0.02). Furthermore, CMPCs increased the vessel density compared to vehicle in the borderzone at the 3 month time-point (221±24 versus 140± 5 vessels/surface unit respectively, p<0.01). Transplantation of CMPCs and CMPC-CM both regenerated cardiac tissue, with the formation of new human cardiomyocytes and vessels.
Conclusions: Injection of human CMPCs or CMPC-CM into the ischemic heart can preserve long-term cardiac function. The cells partially regenerate the damaged myocardial tissue by forming the necessary cell types Importantly, the infarcted heart provides the required signals to drive the differentiation of CMPCs, excluding the need for time-consuming in vitro differentiation protocols. Therefore, human CMPCs are a promising candidate for cell-based therapy.