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.