title: 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: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Sonya B
authors: SB
authors: Sonnenberg
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Aboli A
authors: AA
authors: Rane
authors: Department of Chemical Engineering, The Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Department of Bioengineering, The Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
authors: Cassie J
authors: CJ
authors: Liu
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Nikhil
authors: N
authors: Rao
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Gillie
authors: G
authors: Agmon
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Sophia
authors: S
authors: Suarez
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Raymond
authors: R
authors: Wang
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Adam
authors: A
authors: Munoz
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Vaibhav
authors: V
authors: Bajaj
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Shirley
authors: S
authors: Zhang
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Rebecca
authors: R
authors: Braden
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Pamela J
authors: PJ
authors: Schup-Magoffin
authors: Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Oi Ling
authors: OL
authors: Kwan
authors: Department of Medicine, University of California, San Diego, La Jolla, CA, USA.
authors: Anthony N
authors: AN
authors: DeMaria
authors: Department of Chemical Engineering, The Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA; Department of Bioengineering, The Stanford Cardiovascular Institute, Stanford University, Stanford, CA, USA.
authors: Jennifer R
authors: JR
authors: Cochran
authors: Department of Bioengineering and Sanford Consortium for Regenerative Medicine, University of California, San Diego, La Jolla, CA, USA. Electronic address: christman@eng.ucsd.edu.
authors: Karen L
authors: KL
authors: Christman
mesh_terms: D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D048429:Cell Size / Q000187:drug effects; D004195:Disease Models, Animal; D016503:Drug Delivery Systems; D005109:Extracellular Matrix / Q000187:drug effects / Q000378:metabolism; D005260:Female; D005355:Fibrosis / Q000473:pathology; D006334:Heart Function Tests; D017228:Hepatocyte Growth Factor / Q000627:therapeutic use*; D006801:Humans; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate / Q000737:chemistry*; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology*; D032383:Myocytes, Cardiac / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000187:drug effects; D010446:Peptide Fragments / Q000494:pharmacology / Q000627:therapeutic use; D015202:Protein Engineering; D019859:Proto-Oncogene Proteins c-met / Q000378:metabolism; D017207:Rats, Sprague-Dawley; D034421:Sus scrofa; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D010446:Peptide Fragments; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met
keywords: Decellularization; Extracellular matrix; Growth factor; Hydrogel; Myocardial infarction