Ischemic heart disease is characterized chronically by a healed infarct, foci of 
myocardial scarring, cavitary dilation, and impaired ventricular performance. 
These alterations can only be reversed by replacement of scarred tissue with 
functionally competent myocardium. We tested whether cardiac progenitor cells 
(CPCs) implanted in proximity of healed infarcts or resident CPCs stimulated 
locally by hepatocyte growth factor and insulin-like growth factor-1 invade the 
scarred myocardium and generate myocytes and coronary vessels improving the 
hemodynamics of the infarcted heart. Hepatocyte growth factor is a powerful 
chemoattractant of CPCs, and insulin-like growth factor-1 promotes their 
proliferation and survival. Injection of CPCs or growth factors led to the 
replacement of approximately 42% of the scar with newly formed myocardium, 
attenuated ventricular dilation and prevented the chronic decline in function of 
the infarcted heart. Cardiac repair was mediated by the ability of CPCs to 
synthesize matrix metalloproteinases that degraded collagen proteins, forming 
tunnels within the fibrotic tissue during their migration across the scarred 
myocardium. New myocytes had a 2n karyotype and possessed 2 sex chromosomes, 
excluding cell fusion. Clinically, CPCs represent an ideal candidate cell for 
cardiac repair in patients with chronic heart failure. CPCs may be isolated from 
myocardial biopsies and, following their expansion in vitro, administered back 
to the same patients avoiding the adverse effects associated with the use of 
nonautologous cells. Alternatively, growth factors may be delivered locally to 
stimulate resident CPCs and promote myocardial regeneration. These forms of 
treatments could be repeated over time to reduce progressively tissue scarring 
and expand the working myocardium.