Abstract
Introduction: The human cardiomyocyte progenitor cell (hCMPC) is part of a population of stem cells located in the human heart. Isolates of hCMPCs from human fetal hearts showed differentiation into functional cardiomyocytes in vitro. In the present study we investigated the potential of hCMPCs to restore ischemic myocardium and improve left ventricular (LV) function in a myocardial infarction (MI) model in mice. Methods: MI was induced in immune-compromised NOD/scid mice, immediately followed by injection of hCMPCs labeled with eGFP (hCMPC group) or vehicle only (control group). From sham operated mice we obtained reference values. Cardiac performance was measured 2 and 14 days after MI using 9.4 Tesla MRI. LV pressure-volume measurements were performed at day 15 followed by extensive immunohistological analysis. Results: Animals injected with hCMPCs after MI demonstrated a significantly higher LV ejection fraction, a lower LV end-systolic volume and a smaller ô (relaxation time constant), compared to animals from the control group (by 17%, by 22% and by 24% respectively, P<0.05). A trend towards a lower LV end-diastolic volume was also observed, although this did not reach significance (P=0.14). Both the infarct zone and border zone of the hCMCP group showed a significant increase in total blood vessel density (6.67%±0.85% and 9.13%±0.46%) compared to control (3.35%±1.13% and 4.31%±1.08%, P<0.01 in either zone). The infarct and border zone of the hearts injected with hCMPCs also had a diminished collagen type III density (1.07±0.06 and 1.11±0.07), compared to the control group (1.45±0.05 and 1.51±0.08, P<0.01 in either zone). Furthermore, nuclear PCNA expression indicated an increased rate of mitosis in the infarct (37.76%±2.23%) and border zone (48.84%±2.07%) compared to the infarct (25.48%±4.83%, P<0.01) and border zone (32.03%±1.03%, P<0.01) of the control group. Conclusions: Fetal hCMPCs engraft into infarcted myocardium where they improve LV systolic function and attenuate ventricular remodeling. Increased blood vessel density, elevated mitosis rate and decreased collagen III deposition may be involved in this process. These results indicate that hCMPCs are promising candidates for cell-based therapy.
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