Modeling atrial fibrosis in vitro—Generation and characterization of a novel human atrial fibroblast cell line

Atrial fibrillation (AF) is regularly accompanied by cardiac fibrosis and concomitant heart failure. Due to the heterogeneous nature and complexity of fibrosis, the knowledge about the underlying mechanisms is limited, which prevents effective pharmacotherapy. A deeper understanding of cardiac fibroblasts is essential to meet this need. We previously described phenotypic and functional differences between atrial fibroblasts from patients in sinus rhythm and with AF. Herein, we established and characterized a novel human atrial fibroblast line, which displays typical fibroblast morphology and function comparable to primary cells but with improved proliferation capacity and low spontaneous myofibroblast differentiation. These traits make our model suitable for the study of fibrosis mechanisms and for drug screening aimed at developing effective antifibrotic pharmacotherapy.
Using lentiviral transfer of Upcyte® proliferation genes, a novel human atrial fibroblast cell line (HAF‐SRK01) was generated. Proliferation was significantly increased and spontaneous myofibroblast differentiation significantly decreased compared to primary cells. Functional analyzes confirmed that the cell line is suitable for recapitulating fibrosis development. These traits predispose the model for antifibrotic drug screening and to study fibrosis mechanisms.