Tanshinone IIA increases recruitment of bone marrow mesenchymal stem cells to infarct region via up-regulating stromal cell-derived factor-1/CXC chemokine receptor 4 axis in a myocardial ischemia model

Systemic administration with bone marrow mesenchymal stem cells (BMSCs) is a promising approach to cure myocardial ischemia (MI), while the efficacy of cell transplantation is limited by the low engraftment of BMSCs. Tanshinone IIA (Tan IIA) has been reported many times for the treatment of MI. Therefore, the present study was performed to investigate whether Tan IIA could increase the migration of BMSCs to ischemic region and its potential mechanisms. In our study, we found that combination treatment with Tan IIA and BMSCs significantly alleviated the infarct size when compared with control group (31.46 ± 3.00% vs. 46.95 ± 6.51%, p < 0.05). Results of real-time PCR showed that Tanshinone IIA (Tan IIA) did increase the migration of BMSCs to ischemic region in vivo, which was correlated with cardiac function recovery after MI. Furthermore, 2 μM Tan IIA could enhance the migration capability of BMSCs in vitro (3.69-fold of control), and this enhancement could be blocked by AMD3100 (a CXC chemokine receptor 4 blocker). CXCR4, together with its specific receptor, stromal cell-derived factor-1 (SDF-1) plays a critical role in the stem cell recruitment. Our experiment indicated that Tan IIA could promote SDF-1α expression in the infarct area and enhance the CXCR4 expression of BMSCs in vitro. Therefore, we postulated that Tan IIA could increase the BMSCs migration via up-regulating SDF1/CXCR4 axis.