Modeling Atrial Fibrillation through Intermittent Tachypacing-Induced Remodeling in hiPSC-Derived Atrial Cardiomyocytes and Atrial Fibroblast

Abstract

BackgroundHuman in vitro models for atrial fibrillation (AF) are limited. Human-induced pluripotent stem cell-derived atrial cardiomyocytes (hiPSC-aCMs) provide a valuable tool to study AF pathophysiology by facilitating in vitro modeling. ObjectivesTo investigate the effects of an intermittent tachypacing protocol (ITPP) in matured hiPSC-aCMs co-cultured with human atrial cardiac fibroblast (haCF) to mimic AF-associated electroanatomical phenotypes. Methods and ResultshiPSC-aCMs were cultured alone or co-cultured with haCFs at 90/10 and 70/30 ratios. ITPP was applied through field stimulation, and optical mapping assessed action potentials (APs) and calcium transients (CaTs). Immunostaining was performed to quantify pro-fibrotic biomarkers (Collagen III and TGF{beta}1). ITPP led to increased spontaneous AP frequency ({Delta}=+31{+/-}7%, P100-fold increase in Collagen III expression (P View larger version (61K): org.highwire.dtl.DTLVardef@1c56760org.highwire.dtl.DTLVardef@105d4a2org.highwire.dtl.DTLVardef@1cb18d4org.highwire.dtl.DTLVardef@cb3353_HPS_FORMAT_FIGEXP M_FIG O_FLOATNOGraphical AbstractC_FLOATNO Human iPSC-Model for Atrial Fibrillation C_FIG