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Sustained Delivery of Insulin-Like Growth Factor-1/Hepatocyte Growth Factor Stimulates Endogenous Cardiac Repair in the Chronic Infarcted Pig Heart

Journal article published in 2014 by Stefan Koudstaal, Maartje M. C. Bastings, Dries A. M. Feyen, Cheryl D. Waring, Fj Frebus van Slochteren, Frebus J. van Slochteren, Frebus J. Slochteren, Pyw Patricia Dankers, Patricia Y. W. Dankers, Daniele Torella, Jpg Joost Sluijter, Joost P. G. Sluijter, Bernardo Nadal-Ginard, Pafm Pieter Doevendans, Pieter A. Doevendans and other authors.
This paper is available in a repository.
This paper is available in a repository.

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Abstract

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.