Abstract 1390: Cardiac Stem Cells Regenerate the Coronary Vasculature and the Scarred Infarcted Myocardium in Rats
Defects in the large, intermediate, and small-size arteries and arterioles, together with segmental and focal myocardial fibrosis characterize end-stage ischemic heart failure in humans. Therefore, two major problems have to be resolved to rebuild the severely damaged decompensated heart: the different segments of the coronary vasculature have to be regenerated and the scarred tissue has to be replaced by functionally competent myocardium. For this purpose, myocardial infarction was produced in rats by permanent ligation of the left coronary artery and clonogenic c-kit-positive cardiac stem cells (CSCs) were injected in proximity of the occluded vessel in an attempt to form a biological bypass and, thereby, improve the vascularization of the distal myocardium. Similarly, CSCs were locally administered at the opposite sides of healed infarcts one month after the initial event. CSCs expressed enhanced green fluorescent protein (EGFP) which was employed as a marker of progeny of the transplanted cells in the recipient heart. One month after treatment, newly formed EGFP-positive coronary arteries with a diameter ranging from 65 to 250 um were detected in the spared myocardium of the base and upper mid-region of the left ventricle (LV). In proximity of the infarct, resistance arterioles, 6–50 um in diameter were identified in combination with numerous capillary profiles. Moreover, the scarred infarct was replaced nearly 50% by regenerated myocardium composed of myocytes varying in size from 300 –10,000 um3. The number of formed myocytes markedly exceeded the number of lost cells, but only 10% of these new myocytes had reached the adult phenotype. The reconstitution of the coronary vasculature was associated with a significant increase in myocardial blood flow within the infarcted myocardium. Hemodynamically, treatment with CSCs led to an improvement in LV systolic pressure, LV developed pressure, LV + and -dP/dt, in combination with a reduction of LV end-diastolic pressure and computed diastolic wall stress. In conclusion, CSCs can restore in part the occluded coronary vessels with new coronary arteries and the healed infarct with functionally competent myocardium improving the cardiomyopathic heart structurally and functionally.