In vitro differentiation of human cardiac fibroblasts into myofibroblasts: characterization using electrical impedance

Abstract

Cardiac arrhythmias represent about 50% of the cardiovascular diseases which are the first cause of mortality in the world. Implantable medical devices play a major role for treating these arrhythmias. Nevertheless the leads induce an unwanted biological phenomenon called fibrosis. This phenomenon begins at a cellular level and is effective at a macroscopic scale causing tissue remodelling with a local modification of the active cardiac tissue. Fibrosis mechanism is complex but at the cellular level, it mainly consists in cardiac fibroblasts activation and differentiation into myofibroblasts. We developed a simplified in vitro model of cardiac fibrosis, with human cardiac fibroblasts whom differentiation into myofibroblasts was promoted with TGF-beta 1. Our study addresses an unreported impedance-based method for real-time monitoring of in vitro cardiac fibrosis. The objective was to study whether the differentiation of cardiac fibroblasts in myofibroblasts had a specific signature on the cell index, an impedance-based feature measured by the xCELLigence system. Primary human cardiac fibroblasts were cultured along 6 days, with or without laminin coating, to study the role of this adhesion protein in cultures long-term maintenance. The cultures were characterized in the presence or absence of TGF-beta 1 and we obtained a significant cell index signature specific to the human cardiac fibroblasts differentiation.