Insulin gene enhancer binding protein 1 induces adipose tissue-derived stem cells to differentiate into pacemaker-like cells

Abstract

Hybrid approaches combining gene- and cell-based therapies to make biological pacemakers are a promising therapeutic avenue for bradyarrhythmia. The present study aimed to direct adipose tissue-derived stem cells (ADSCs) to differentiate specifically into cardiac pacemaker cells by overexpressing a single transcription factor, insulin gene enhancer binding protein 1 (ISL-1). In the present study, the ADSCs were transfected with ISL-1 or mCherry fluorescent protein lentiviral vectors and co-cultured with neonatal rat ventricular cardiomyocytes (NRVMs) in vitro for 5-7 days. The feasibility of regulating the differentiation of ADSCs into pacemaker-like cells by overexpressing ISL-1 was evaluated by observation of cell morphology and beating rate, reverse transcription-quantitative polymerase chain reaction analysis, western blotting, immunofluorescence and analysis of electrophysiological activity. In conclusion, these data indicated that the overexpression of ISL-1 in ADSCs may enhance the pacemaker phenotype and automaticity in vitro, features which were significantly increased following co-culture induction.