title: Sustained delivery of insulin-like growth factor-1/hepatocyte growth factor stimulates endogenous cardiac repair in the chronic infarcted pig heart.
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.
authors.affiliation: Department of Cardiology, Division Heart and Lungs, University Medical Center Utrecht, Room E03.511, PO Box 85500, 3508 GA, Utrecht, The Netherlands.
authors.forename: Stefan
authors.initials: S
authors.lastname: Koudstaal
authors.forename: Maartje M C
authors.initials: MM
authors.lastname: Bastings
authors.forename: Dries A M
authors.initials: DA
authors.lastname: Feyen
authors.forename: Cheryl D
authors.initials: CD
authors.lastname: Waring
authors.forename: Frebus J
authors.initials: FJ
authors.lastname: van Slochteren
authors.forename: Patricia Y W
authors.initials: PY
authors.lastname: Dankers
authors.forename: Daniele
authors.initials: D
authors.lastname: Torella
authors.forename: Joost P G
authors.initials: JP
authors.lastname: Sluijter
authors.forename: Bernardo
authors.initials: B
authors.lastname: Nadal-Ginard
authors.forename: Pieter A
authors.initials: PA
authors.lastname: Doevendans
authors.forename: Georgina M
authors.initials: GM
authors.lastname: Ellison
authors.forename: Steven A J
authors.initials: SA
authors.lastname: Chamuleau
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000188:drug therapy / Q000473:pathology / Q000503:physiopathology; D049109:Cell Proliferation / Q000187:drug effects; D004195:Disease Models, Animal; D004343:Drug Implants; D005260:Female; D005355:Fibrosis; D017228:Hepatocyte Growth Factor / Q000008:administration & dosage*; D020100:Hydrogels; D015552:Injections, Intralesional; D007334:Insulin-Like Growth Factor I / Q000008:administration & dosage*; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D020127:Recovery of Function; D012038:Regeneration / Q000187:drug effects*; D013234:Stem Cells / Q000187:drug effects* / Q000473:pathology; D013552:Swine; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: D004343:Drug Implants; D020100:Hydrogels; D017228:Hepatocyte Growth Factor; D007334:Insulin-Like Growth Factor I