A new combination of transcription factors increases the harvesting efficiency of pacemaker-like cells

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.