Sustained delivery of insulin-Like growth factor-1/hepatocyte growth factor stimulates endogenous cardiac repair in the chronic infarcted pig heart

S. Koudstaal, M.M.C. Bastings, D. Feyen, C.D. Waring, F.J. van Slochteren, P.Y.W. Dankers, D. Torella, J.P.G. Sluijter, B. Nadal Ginard, P.A.F.M. Doevendans, G.M. Ellison, S.A.J. Chamuleau

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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.
Original languageEnglish
Pages (from-to)232-241
JournalJournal of Cardiovascular Translational Research
Volume7
Issue number2
DOIs
Publication statusPublished - 2014

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    Koudstaal, S., Bastings, M. M. C., Feyen, D., Waring, C. D., van Slochteren, F. J., Dankers, P. Y. W., Torella, D., Sluijter, J. P. G., Nadal Ginard, B., Doevendans, P. A. F. M., Ellison, G. M., & Chamuleau, S. A. J. (2014). Sustained delivery of insulin-Like growth factor-1/hepatocyte growth factor stimulates endogenous cardiac repair in the chronic infarcted pig heart. Journal of Cardiovascular Translational Research, 7(2), 232-241. https://doi.org/10.1007/s12265-013-9518-4