Comparison of mouse brown and white adipose-derived stem cell differentiation into pacemaker-like cells induced by TBX18 transduction

Abstract

The present study aimed to compare brown adipose-derived stem cell (BASC) and white adipose-derived stem cell (WASC) differentiation into pacemaker-like cells following T-box (TBX)18 transduction. Mouse BASCs and WASCs were induced to differentiate into pacemaker-like cells by adenovirus-TBX18 transduction in vitro. The transduction rate was determined by fluorescence microscopy and cell ultrastructural changes were observed by transmission electron microscopy at 48 h post-transduction. The mRNA and protein expression of pacemaker cell-associated markers, including TBX18, TBX3, sarcomeric α-actinin (Sr) and hyperpolarization-activated cyclic nucleotide-gated channel 4 (HCN4), were detected by reverse transcription-quantitative polymerase chain reaction, immunofluorescence staining and western blot analysis. The results demonstrated that no significant difference was observed in the transduction rate between BASCs and WASCs. The ultrastructure of BASCs was observed to be more complex than that of WASCs, indicating that BASCs may possess a better structural foundation to differentiate into pacemaker-like cells. TBX18, TBX3, Sr and HCN4 mRNA and protein expression in differentiated stem cells was significantly increased compared with the respective control groups. Furthermore, the expression levels were significantly higher in TBX18-BASCs compared with TBX18-WASCs. In conclusion, TBX18 gene transduction may facilitate the differentiation of BASCs and WASCs into pacemaker-like myocardial cells, and BASCs may have a higher capacity than WASCs for this differentiation. TBX18 gene may therefore act as an efficient candidate in cell transplantation therapy for diseases and for future research into the cardiovascular system.