Ascorbic acid induces cardiac differentiation of white adipose tissue-derived stem cells.

White adipose tissue (WAT) is the bulk of fatty tissues in humans. Enhancing the potential of WAT-derived stem cells (WATDCs) to generate cardiomyocytes may help supply sufficient number of therapeutically potent cells for heart repair in vivo. Therefore, we investigated whether ascorbic acid (AA) could facilitate the cardiac differentiation of WATDCs and the underlying mechanisms. Our results indicated that AA dose-dependently stimulates the cardiac differentiation of WATDCs, which is supported by the up-regulated expression of cardiac markers and the appearance of myotube-like cell morphologies. Time-course study showed that the front phase (0-4 days) is crucial for the action of AA on cardiac differentiation, which hints that AA may take effect through enhancing the proliferation of cardiac progenitor cells. EdU assay ascertained AA indeed promotes cell growth dose-dependently in the front phase. Further investigation indicated that AA induces the phosphorylation of MEK and ERK, and the synthesis of collagen I (Col I). Interference of MEK/ERK activity or Col I synthesis blocks the cardiomyogenic activity of AA in WATDCs. These findings demonstrated that AA facilitates WATDC cardiogenesis via promoting the proliferation of cardiac progenitor cells through MEK/ERK signaling and collagen synthesis.