Abstract
Biological pacemakers that combine cell‑based and gene‑based therapies are a promising treatment for sick sinus syndrome or severe atrioventricular block. The current study aimed to induce differentiation of adipose tissue‑derived stem cells (ADSCs) into cardiac pacemaker cells through co‑expression of the transcription factors insulin gene enhancer binding protein 1 (ISL‑1) and T‑box18 (Tbx18). ADSCs were transfected with green fluorescent protein, ISL‑1, Tbx18 or ISL‑1+Tbx18 fluorescent protein lentiviral vectors, and subsequently co‑cultured with neonatal rat ventricular cardiomyocytes in vitro for 7 days. The potential for regulating the differentiation of ADSCs into pacemaker‑like cells was evaluated by cell morphology, beating rate, reverse transcription‑quantitative polymerase chain reaction, western blotting, immunofluorescence and electrophysiological activity. ADSCs were successfully transformed into spontaneously beating cells that exhibited a behavior similar to that of co‑cultured pacemaker cells. This effect was significantly increased in the combined ISL‑1 and Tbx18 group. These results provide a potential strategy for enriching the cardiac pacemaker cell population from ADSCs.