Injectable Myocardial Matrix Hydrogel Mitigates Negative Left Ventricular Remodeling in a Chronic Myocardial Infarction Model

Miranda D Diaz; Elaine Tran; Martin Spang; Raymond Wang; Roberto Gaetani; Colin G Luo; Rebecca Braden; Ryan C Hill; Kirk C Hansen; Anthony N DeMaria; Karen L Christman

doi:10.1016/j.jacbts.2021.01.003

Injectable Myocardial Matrix Hydrogel Mitigates Negative Left Ventricular Remodeling in a Chronic Myocardial Infarction Model

JACC Basic Transl Sci. 2021 Mar 10;6(4):350-361. doi: 10.1016/j.jacbts.2021.01.003. eCollection 2021 Apr.

Authors

Miranda D Diaz^{1

2}, Elaine Tran^{1

2}, Martin Spang^{1

2}, Raymond Wang^{1

2}, Roberto Gaetani^{1

2

3}, Colin G Luo^{1

2}, Rebecca Braden^{1

2}, Ryan C Hill⁴, Kirk C Hansen⁴, Anthony N DeMaria⁵, Karen L Christman^{1

2}

Affiliations

¹ Department of Bioengineering, University of California, San Diego, La Jolla, California, USA.
² Sanford Consortium for Regenerative Medicine, La Jolla, California, USA.
³ Department of Molecular Medicine, Sapienza University of Rome, Rome, Italy.
⁴ Department of Biochemistry and Molecular Genetics, Anschutz Medical Campus, University of Colorado, Aurora, Colorado, USA.
⁵ Department of Medicine, University of California, San Diego, La Jolla, California, USA.

Abstract

A first-in-man clinical study on a myocardial-derived decellularized extracellular matrix hydrogel suggested the potential for efficacy in chronic myocardial infarction (MI) patients. However, little is understood about the mechanism of action in chronic MI. In this study, the authors investigated the efficacy and mechanism by which the myocardial matrix hydrogel can mitigate negative left ventricular (LV) remodeling in a rat chronic MI model. Assessment of cardiac function via magnetic resonance imaging demonstrated preservation of LV volumes and apical wall thickening. Differential gene expression analyses showed the matrix is able to prevent further negative LV remodeling in the chronic MI model through modulation of the immune response, down-regulation of pathways involved in heart failure progression and fibrosis, and up-regulation of genes important for cardiac muscle contraction.

Keywords: CMR, cardiac magnetic resonance; ECM, extracellular matrix; EDV, end-diastolic volume; EF, ejection fraction; ESV, end-systolic volume; HF, heart failure; IHC, immunohistochemistry; KEGG, Kyoto Encyclopedia of Genes and Genomes; LV, left ventricular; MI, myocardial infarction; MS, mass spectrometry; QconCAT, quantitative concatamer; biomaterials; chronic inflammation; chronic myocardial infarction; gene expression.

Abstract

Grants and funding