Extracellular matrix remodeling following myocardial infarction influences the therapeutic potential of mesenchymal stem cells

• DOI: 10.1186/scrt403
• Publication Date: 2014-01-24T10:01:44Z
• Authors: Kelly Elizabeth S...; Kyle Patrick Quinn; Katherine Michele...; Irene Georgakoudi; Lauren Deems Black
• Keywords: Homeodomain Proteins; Male; 0303 health sciences; Hepatocyte Growth Factor; Research; Myocardial Infarction; Cell Differentiation; Mesenchymal Stem Cells; Mesenchymal Stem Cell Transplantation; Chemokine CXCL12; Extracellular Matrix; GATA4 Transcription Factor; Rats; Rats, Sprague-Dawley; 03 medical and health sciences; Paracrine Communication; Homeobox Protein Nkx-2.5; Animals; Myocytes, Cardiac; Cells, Cultured; Transcription Factors

Abstract Introduction Although stem cell therapy is a promising treatment for myocardial infarction, the minimal functional improvements observed clinically limit its widespread application. A need exists to maximize therapeutic potential of these cells by first understanding what factors within infarct microenvironment affect their ability regenerate necrotic tissue. In this study, we assessed both differentiation capacity and paracrine signaling as function extracellular matrix remodeling after infarction. Methods Mechanical compositional changes decellularized infarcted myocardium were characterized understand how environment, specifically, was altered time coronary artery ligation in Sprague–Dawley rats. These alterations modeled polyacrylamide gel system variables composition stiffness drive mesenchymal towards cardiac lineage. Finally, secretome through gene protein expression conditioned media studies. Results The tissue revealed significant mechanical properties ECM with following This dynamically regulates early differentiation. Whereas Nkx2.5 limited presence chronic remodeled increased stiffness, GATA4 enhanced. addition, promotes several proangiogenic, prosurvival, antifibrotic, immunomodulatory growth factors. particular, an increase HGF SDF1 secretion can rescue oxidatively stressed cardiomyocytes vitro . Conclusions study demonstrated that decellularization diseased allows exclusive analysis influence significantly cellular phenotype. Characterization fate infarction critical developing ideal strategy implantation regeneration ultimately reduce prevalence severity heart failure.