Delivery of an engineered HGF fragment in an extracellular matrix-derived hydrogel prevents negative LV remodeling post-myocardial infarction.

Abstract

Hepatocyte growth factor (HGF) has been shown to have anti-fibrotic, pro-angiogenic, and cardioprotective effects; however, it is highly unstable and expensive to manufacture, hindering its clinical translation. Recently, a HGF fragment (HGF-f), an alternative c-MET agonist, was engineered to possess increased stability and recombinant expression yields. In this study, we assessed the potential of HGF-f, delivered in an extracellular matrix (ECM)-derived hydrogel, as a potential treatment for myocardial infarction (MI). HGF-f protected cardiomyocytes from serum-starvation and induced down-regulation of fibrotic markers in whole cardiac cell isolate compared to the untreated control. The ECM hydrogel prolonged release of HGF-f compared to collagen gels, and in vivo delivery of HGF-f from ECM hydrogels mitigated negative left ventricular (LV) remodeling, improved fractional area change (FAC), and increased arteriole density in a rat myocardial infarction model. These results indicate that HGF-f may be a viable alternative to using recombinant HGF, and that an ECM hydrogel can be employed to increase growth factor retention and efficacy.

• Authors: Sonya B Sonnenberg, Aboli A Rane, Cassie J Liu, Nikhil Rao, Gillie Agmon, Sophia Suarez, Raymond Wang, Adam Munoz, Vaibhav Bajaj, Shirley Zhang, Rebecca Braden, Pamela J Schup-Magoffin, Oi Ling Kwan, Anthony N DeMaria, Jennifer R Cochran, Karen L Christman
• Journal: Biomaterials (Biomaterials) Vol. 45 Pg. 56-63 (Mar 2015) ISSN: 1878-5905 [Electronic] Netherlands
• PMID: 25662495 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
• Copyright: Copyright © 2015 Elsevier Ltd. All rights reserved.

Chemical References

• Peptide Fragments
• Hydrogel, Polyethylene Glycol Dimethacrylate
• Hepatocyte Growth Factor
• Proto-Oncogene Proteins c-met

Topics

• Animals
• Blood Vessels (drug effects, pathology)
• Cell Size (drug effects)
• Disease Models, Animal
• Drug Delivery Systems
• Extracellular Matrix (drug effects, metabolism)
• Female
• Fibrosis (pathology)
• Heart Function Tests
• Hepatocyte Growth Factor (therapeutic use)
• Humans
• Hydrogel, Polyethylene Glycol Dimethacrylate (chemistry)
• Myocardial Infarction (diagnostic imaging, drug therapy, pathology, physiopathology)
• Myocytes, Cardiac (pathology)
• Myocytes, Smooth Muscle (metabolism)
• Neovascularization, Physiologic (drug effects)
• Peptide Fragments (pharmacology, therapeutic use)
• Protein Engineering
• Proto-Oncogene Proteins c-met (metabolism)
• Rats, Sprague-Dawley
• Sus scrofa
• Ultrasonography
• Ventricular Remodeling (drug effects)