BACKGROUND: Cardiac progenitor cells (CPCs) possess the insulin-like growth 
factor-1 (IGF-1)-IGF-1 receptor system, and IGF-1 can be tethered to 
self-assembling peptide nanofibers (NF-IGF-1), leading to prolonged release of 
this growth factor to the myocardium. Therefore, we tested whether local 
injection of clonogenic CPCs and NF-IGF-1 potentiates the activation and 
differentiation of delivered and resident CPCs enhancing cardiac repair after 
infarction.
METHODS AND RESULTS: Myocardial infarction was induced in rats, and untreated 
infarcts and infarcts treated with CPCs or NF-IGF-1 only and CPCs and NF-IGF-1 
together were analyzed. With respect to infarcts exposed to CPCs or NF-IGF-1 
alone, combination therapy resulted in a greater increase in the ratio of left 
ventricular mass to chamber volume and a better preservation of +dP/dt, -dP/dt, 
ejection fraction, and diastolic wall stress. Myocardial regeneration was 
detected in all treated infarcts, but the number of newly formed myocytes with 
combination therapy was 32% and 230% higher than with CPCs and NF-IGF-1, 
respectively. Corresponding differences in the volume of regenerated myocytes 
were 48% and 115%. Similarly, the length density of newly formed coronary 
arterioles with both CPCs and NF-IGF-1 was 73% and 83% greater than with CPCs 
and NF-IGF-1 alone, respectively. Importantly, activation of resident CPCs by 
paracrine effects contributed to cardiomyogenesis and vasculogenesis. 
Collectively, CPCs and NF-IGF-1 therapy reduced infarct size more than CPCs and 
NF-IGF-1 alone.
CONCLUSIONS: The addition of nanofiber-mediated IGF-1 delivery to CPC therapy 
improved in part the recovery of myocardial structure and function after 
infarction.