Objective: icCDCs improve function of ischemic myocardium and increase cardiomyocyte nuclear density but the extent to which this is explained by an increase in nuclei per cell vs. the formation of new myocytes is unclear. We aimed to address this issue and quantify new myocyte formation throughout the left ventricle (LV) after global icCDC treatment in swine with hibernating myocardium.
Methods: Swine with a chronic LAD stenosis (N=29) received either ~35 x 106 icCDCs or no treatment. Regional function (echocardiography) and myocyte morphometric indices were assessed 1 month later. Transverse and longitudinal tissue sections were used to measure regional myocyte nuclear density, diameter, length, and nuclei/cell, from which myocyte volume and myocytes per gram of myocardium were calculated.
Results: icCDC-mediated improvements in regional function were accompanied by an increase in myocyte nuclear density without a change in the number of nuclei/cell (Table). Compared with untreated animals, icCDC-treated animals exhibited a reduction in myocyte volume and a reciprocal increase in the number of myocytes per gram of tissue. Anatomic LV hypertrophy did not occur, however, as LV mass/body mass ratio was not different between groups (untreated: 2.5 ± 0.1 vs. icCDCs: 2.3 ± 0.1).
Conclusion: These data demonstrate that icCDCs produce significant myocyte regeneration throughout the regionally ischemic heart that is dissociated from alterations in LV mass. Changes in myocyte nuclear density do not reflect an altered number of nuclei/cell and quantitative estimates suggest that intracoronary delivery of CDCs to the entire LV increases the number of myocytes by ~25% in just 4 weeks.