Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction.

نویسندگان

  • M Elena Padin-Iruegas
  • Yu Misao
  • Michael E Davis
  • Vincent F M Segers
  • Grazia Esposito
  • Tomotake Tokunou
  • Konrad Urbanek
  • Toru Hosoda
  • Marcello Rota
  • Piero Anversa
  • Annarosa Leri
  • Richard T Lee
  • Jan Kajstura
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Local myocardial insulin-like growth factor 1 (IGF-1) delivery with biotinylated peptide nanofibers improves cell therapy for myocardial infarction.

Strategies for cardiac repair include injection of cells, but these approaches have been hampered by poor cell engraftment, survival, and differentiation. To address these shortcomings for the purpose of improving cardiac function after injury, we designed self-assembling peptide nanofibers for prolonged delivery of insulin-like growth factor 1 (IGF-1), a cardiomyocyte growth and differentiatio...

متن کامل

Simultaneous delivery of Wharton’s jelly mesenchymal stem cells and insulin-like growth factor-1 in acute myocardial infarction

Wharton’s jelly mesenchymal stem cells (HWJMSCs) hold promise for myocardial regeneration, but optimal treatment regimen (preferably with a growth factor) is required to maximize functional benefits. The aim of this study was to explore the cardioprotective and angiogenesis effects of HWJMSCs combined with insulin-like growth factor-1 (IGF-1) in the treatment of acute myocardial infarction. Th...

متن کامل

Ischemia-Reperfusion Injury and Pregnancy Initiate Time-Dependent and Robust Signs of Up-Regulation of Cardiac Progenitor Cells

To explore how cardiac regeneration and cell turnover adapts to disease, different forms of stress were studied for their effects on the cardiac progenitor cell markers c-Kit and Isl1, the early cardiomyocyte marker Nkx2.5, and mast cells. Adult female rats were examined during pregnancy, after myocardial infarction and ischemia-reperfusion injury with/out insulin like growth factor-1(IGF-1) an...

متن کامل

Simultaneous delivery of Wharton’s jelly mesenchymal stem cells and insulin-like growth factor-1 in acute myocardial infarction

Wharton’s jelly mesenchymal stem cells (HWJMSCs) hold promise for myocardial regeneration, but optimal treatment regimen (preferably with a growth factor) is required to maximize functional benefits. The aim of this study was to explore the cardioprotective and angiogenesis effects of HWJMSCs combined with insulin-like growth factor-1 (IGF-1) in the treatment of acute myocardial infarction. Th...

متن کامل

Exercise for the heart: signaling pathways

Physical exercise, a potent functional intervention in protecting against cardiovascular diseases, is a hot topic in recent years. Exercise has been shown to reduce cardiac risk factors, protect against myocardial damage, and increase cardiac function. This improves quality of life and decreases mortality and morbidity in a variety of cardiovascular diseases, including myocardial infarction, ca...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Circulation

دوره 120 10  شماره 

صفحات  -

تاریخ انتشار 2009