Guanxin Danshen Formulation improved the effect of mesenchymal stem cells transplantation for the treatment of myocardial infarction probably via enhancing the engraftment

Abstract

Although intravenous injection is the most convenient and feasible approach for mesenchymal stem cells (MSCs) delivery, the proportion of donor stem cells in the target myocardium after transplantation is small. It is believed that TCM enhances the effect of stem cell therapy by improving the hostile microenvironment and promoting the migration and survival of stem cells. Guanxin Danshen (GXDS) formulation is one of the main prescriptions for clinical treatment of ischemic heart diseases in China. The purpose of this study was to evaluate the effects of GXDS formulation administration combined with MSCs transplantation on cardiac function improvement, apoptosis, angiogenesis and survival of transplanted cells in an acute model of acute myocardial infarction (MI). After being labeled with GFP, MSCs were transplanted via intravenous injection. Meanwhile, GXDS dripping pills were given by intragastric administration for 4 weeks from 2 days before MI. Echocardiography showed moderate improvement in cardiac function after administration of GXDS formulation or intravenous transplantation of MSCs. However, GXDS formulation combined with MSCs transplantation significantly improved cardiac function after MI. The myocardial infarct size in rats treated with MSCs was similar to that in rats treated with GXDS formulation. However, GXDS formulation combined with MSCs transplantation significantly reduced infarction area. In addition, GXDS formulation combined with MSCs transplantation not only decreased cell apoptosis according to the TUNEL staining, but also enhanced angiogenesis in the peri-infarction and infarction area. Interestingly, the use of GXDS formulation increased the number of injected MSCs in the infarct area. Furthermore, GXDS formulation combined with MSCs transplantation increased SDF-1 levels in the infarcted area, but did not affect the expression of YAP. Our study provided a more feasible and accessible strategy to enhance the migration of stem cells after intravenous injection by oral administration of GXDS formulation. The combination of GXDS formulation and stem cell therapy has practical significance and application prospects in the treatment of ischemic cardiomyopathy such as MI.

Keywords: Intravenous injection; Mesenchymal stem cells; Myocardial infarction; Stromal cell-derived factor-1; Traditional Chinese medicine.