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

M. Elena Padin-Iruega, 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

Research output: Contribution to journalArticle

161 Citations (Scopus)

Abstract

Cardiac progenitor cells (CPCs) possess the insulin-like growth factor-1 (IGF-I)-IGF-I receptor system, and IGF-I can be tethered to self-assembling peptide nanofibers (NF-IGF-I), leading to prolonged release of this growth factor to the myocardium. Therefore, we tested whether local injection of clonogenic CPCs and NF-IGF-I 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-I 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.

Original languageEnglish
Pages (from-to)876-887
Number of pages12
JournalCirculation
Volume120
Issue number10
DOIs
Publication statusPublished - Nov 17 2009
Externally publishedYes

Fingerprint

Nanofibers
Somatomedins
Insulin-Like Growth Factor I
Infarction
Regeneration
Stem Cells
Muscle Cells
IGF Type 1 Receptor
Arterioles
Cell- and Tissue-Based Therapy

All Science Journal Classification (ASJC) codes

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction. / Padin-Iruega, M. Elena; Misao, Yu; Davis, Michael E.; Segers, Vincent F.M.; Esposito, Grazia; Tokunou, Tomotake; Urbanek, Konrad; Hosoda, Toru; Rota, Marcello; Anversa, Piero; Leri, Annarosa; Lee, Richard T.; Kajstura, Jan.

In: Circulation, Vol. 120, No. 10, 17.11.2009, p. 876-887.

Research output: Contribution to journalArticle

Padin-Iruega, ME, Misao, Y, Davis, ME, Segers, VFM, Esposito, G, Tokunou, T, Urbanek, K, Hosoda, T, Rota, M, Anversa, P, Leri, A, Lee, RT & Kajstura, J 2009, 'Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction', Circulation, vol. 120, no. 10, pp. 876-887. https://doi.org/10.1161/CIRCULATIONAHA.109.852285
Padin-Iruega, M. Elena ; Misao, Yu ; Davis, Michael E. ; Segers, Vincent F.M. ; Esposito, Grazia ; Tokunou, Tomotake ; Urbanek, Konrad ; Hosoda, Toru ; Rota, Marcello ; Anversa, Piero ; Leri, Annarosa ; Lee, Richard T. ; Kajstura, Jan. / Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction. In: Circulation. 2009 ; Vol. 120, No. 10. pp. 876-887.
@article{1af3398a422b49d48b3537532f79336d,
title = "Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction",
abstract = "Cardiac progenitor cells (CPCs) possess the insulin-like growth factor-1 (IGF-I)-IGF-I receptor system, and IGF-I can be tethered to self-assembling peptide nanofibers (NF-IGF-I), leading to prolonged release of this growth factor to the myocardium. Therefore, we tested whether local injection of clonogenic CPCs and NF-IGF-I 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-I 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.",
author = "Padin-Iruega, {M. Elena} and Yu Misao and Davis, {Michael E.} and Segers, {Vincent F.M.} and Grazia Esposito and Tomotake Tokunou and Konrad Urbanek and Toru Hosoda and Marcello Rota and Piero Anversa and Annarosa Leri and Lee, {Richard T.} and Jan Kajstura",
year = "2009",
month = "11",
day = "17",
doi = "10.1161/CIRCULATIONAHA.109.852285",
language = "English",
volume = "120",
pages = "876--887",
journal = "Circulation",
issn = "0009-7322",
publisher = "Lippincott Williams and Wilkins",
number = "10",

}

TY - JOUR

T1 - Cardiac progenitor cells and biotinylated insulin-like growth factor-1 nanofibers improve endogenous and exogenous myocardial regeneration after infarction

AU - Padin-Iruega, M. Elena

AU - Misao, Yu

AU - Davis, Michael E.

AU - Segers, Vincent F.M.

AU - Esposito, Grazia

AU - Tokunou, Tomotake

AU - Urbanek, Konrad

AU - Hosoda, Toru

AU - Rota, Marcello

AU - Anversa, Piero

AU - Leri, Annarosa

AU - Lee, Richard T.

AU - Kajstura, Jan

PY - 2009/11/17

Y1 - 2009/11/17

N2 - Cardiac progenitor cells (CPCs) possess the insulin-like growth factor-1 (IGF-I)-IGF-I receptor system, and IGF-I can be tethered to self-assembling peptide nanofibers (NF-IGF-I), leading to prolonged release of this growth factor to the myocardium. Therefore, we tested whether local injection of clonogenic CPCs and NF-IGF-I 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-I 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.

AB - Cardiac progenitor cells (CPCs) possess the insulin-like growth factor-1 (IGF-I)-IGF-I receptor system, and IGF-I can be tethered to self-assembling peptide nanofibers (NF-IGF-I), leading to prolonged release of this growth factor to the myocardium. Therefore, we tested whether local injection of clonogenic CPCs and NF-IGF-I 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-I 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.

UR - http://www.scopus.com/inward/record.url?scp=70349783458&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70349783458&partnerID=8YFLogxK

U2 - 10.1161/CIRCULATIONAHA.109.852285

DO - 10.1161/CIRCULATIONAHA.109.852285

M3 - Article

C2 - 19704095

AN - SCOPUS:70349783458

VL - 120

SP - 876

EP - 887

JO - Circulation

JF - Circulation

SN - 0009-7322

IS - 10

ER -