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(Circulation. 2009;120:876-887.)
© 2009 American Heart Association, Inc.

Molecular Cardiology

Cardiac Progenitor Cells and Biotinylated Insulin-Like Growth Factor-1 Nanofibers Improve Endogenous and Exogenous Myocardial Regeneration After Infarction

M. Elena Padin-Iruegas, MD^*; Yu Misao, MD^*; Michael E. Davis, PhD; Vincent F.M. Segers, MD, PhD; Grazia Esposito, PhD; Tomotake Tokunou, MD, PhD; Konrad Urbanek, MD; Toru Hosoda, MD, PhD; Marcello Rota, PhD; Piero Anversa, MD; Annarosa Leri, MD; Richard T. Lee, MD; Jan Kajstura, PhD

From the Departments of Anesthesia and Medicine and Cardiovascular Division, Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass.

Correspondence to Jan Kajstura, PhD, Departments of Anesthesia and Medicine, 75 Francis St, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA 02115. E-mail jkajstura{at}partners.org

Received January 20, 2009; accepted June 18, 2009.

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.

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