Ginsenoside-Rg1 mediates microenvironment-dependent endothelial differentiation of human mesenchymal stem cells in vitro

Abstract

Bone marrow-derived mesenchymal stem cells (MSCs) possess a multi-lineage differentiation potential and have the ability to repair and rebuild injured vessels. The autologous differentiated MSC transplantation also makes possible the tissue-engineered grafts. Therefore, the efficient endothelial differentiation of MSCs could be beneficial in the successful injured vessel repair and engraftment. Ginsenoside-Rg1, the most prevalent active constituent of ginseng, is a potent proangiogenic factor of vascular endothelial cells and also has the ability to enhance the proliferation of bone marrow cells. The aim of this study is to investigate the role of ginsenoside-Rg1 in the microenvironment-dependent endothelial differentiation of human MSCs (hMSCs) in vitro. The endothelial differentiation environment was established by co-culturing hMSCs with mature endothelial cells (human umbilical vein endothelial cells) indirectly in vitro. Reverse transcriptase-polymerase chain reaction analysis and fluorescence immunocytochemistry showed a strong expression of endothelial-specific markers such as CD31, Von Willebrand factor, and VE-cadherin. Electron microscopy showed the endothelial characteristic Weibel–Palade bodies of differentiated hMSCs. The increased expression of CD31 demonstrated that Rg1 promoted the endothelial differentiation of hMSCs. The findings here show the differentiation of hMSCs into cells with phenotypic features of endothelial cells using indirect co-culture with mature endothelial cells and provide the evidence that ginsenoside-Rg1 can promote the milieu-dependent endothelial differentiation of hMSCs in vitro.