Delivery of an engineered HGF fragment in an extracellular matrix-derived hydrogel prevents negative LV remodeling post-myocardial infarction. (March 2015)

• Record Type: Journal Article
• Authors: Sonnenberg, Sonya B.; Rane, Aboli A.; Liu, Cassie J.; Rao, Nikhil; Agmon, Gillie; Suarez, Sophia; Wang, Raymond; Munoz, Adam; Bajaj, Vaibhav; Zhang, Shirley; Braden, Rebecca; Schup-Magoffin, Pamela J.; Kwan, Oi Ling; DeMaria, Anthony N.; Cochran, Jennifer R.; Christman, Karen L.
• Is Part Of: Biomaterials. Volume 45(2015)
• Page Start: 56
• Page End: 63
• Publication Date: 2015-03
• Subjects: Myocardial infarction -- Growth factor -- Extracellular matrix -- Decellularization -- Hydrogel; Biomedical materials -- Periodicals; Biocompatible Materials -- Periodicals; Biomatériaux -- Périodiques; 610.28
• DOI: 10.1016/j.biomaterials.2014.12.021
• Languages: English
• ISSNs: 0142-9612

Abstract

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.