TY - JOUR
T1 - Sustained delivery of insulin-like growth factor-1/hepatocyte growth factor stimulates endogenous cardiac repair in the chronic infarcted pig heart
AU - Koudstaal, Stefan
AU - Bastings, Maartje M. C.
AU - Feyen, Dries A. M.
AU - Waring, Cheryl D.
AU - van Slochteren, Frebus J.
AU - Dankers, Patricia Y. W.
AU - Torella, Daniele
AU - Sluijter, Joost P. G.
AU - Nadal-Ginard, Bernardo
AU - Doevendans, Pieter A.
AU - Ellison, Georgina M.
AU - Chamuleau, Steven A. J.
PY - 2014
Y1 - 2014
N2 - Activation of endogenous cardiac stem/progenitor cells (eCSCs) can improve cardiac repair after acute myocardial infarction. We studied whether the in situ activation of eCSCs by insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) could be increased using a newly developed hydrogel in chronic myocardial infarction (MI). One-month post-MI pigs underwent NOGA-guided intramyocardial injections of IGF-1/HGF (GF: both 0.5 μg/mL, n=5) or IGF-1/HGF incorporated in UPy hydrogel (UPy-GF; both 0.5 μg/mL, n=5). UPy hydrogel without added growth factors was administered to four control (CTRL) pigs. Left ventricular ejection fraction was increased in the UPy-GF and GF animals compared to CTRLs. UPy-GF delivery reduced pathological hypertrophy, led to the formation of new, small cardiomyocytes, and increased capillarization. The eCSC population was increased almost fourfold in the border zone of the UPy-GF-treated hearts compared to CTRL hearts. These results show that IGF-1/HGF therapy led to an improved cardiac function in chronic MI and that effect size could be further increased by using UPy hydrogel. © 2014 The Author(s).
AB - Activation of endogenous cardiac stem/progenitor cells (eCSCs) can improve cardiac repair after acute myocardial infarction. We studied whether the in situ activation of eCSCs by insulin-like growth factor 1 (IGF-1) and hepatocyte growth factor (HGF) could be increased using a newly developed hydrogel in chronic myocardial infarction (MI). One-month post-MI pigs underwent NOGA-guided intramyocardial injections of IGF-1/HGF (GF: both 0.5 μg/mL, n=5) or IGF-1/HGF incorporated in UPy hydrogel (UPy-GF; both 0.5 μg/mL, n=5). UPy hydrogel without added growth factors was administered to four control (CTRL) pigs. Left ventricular ejection fraction was increased in the UPy-GF and GF animals compared to CTRLs. UPy-GF delivery reduced pathological hypertrophy, led to the formation of new, small cardiomyocytes, and increased capillarization. The eCSC population was increased almost fourfold in the border zone of the UPy-GF-treated hearts compared to CTRL hearts. These results show that IGF-1/HGF therapy led to an improved cardiac function in chronic MI and that effect size could be further increased by using UPy hydrogel. © 2014 The Author(s).
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=84896403379&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/24395494
U2 - https://doi.org/10.1007/s12265-013-9518-4
DO - https://doi.org/10.1007/s12265-013-9518-4
M3 - Article
C2 - 24395494
SN - 1937-5387
VL - 7
SP - 232
EP - 241
JO - Journal of cardiovascular translational research
JF - Journal of cardiovascular translational research
IS - 2
ER -