Endothelium oriented differentiation of bone marrow mesenchymal stem cells under chemical and mechanical stimulations

Bone marrow mesenchymal stem cells (MSCs) have multi-differentiation capability. Their endothelial cell (EC) oriented differentiation is the key to vasculogenesis, in which both mechanical and chemical stimulations play important roles. Most previous studies reported individual effects of VEGF or fluid shear stress (SS), when MSCs were subjected to shear stress of 10-15 dyn/cm(2) over 24hr. In this paper, we investigated responses of MSCs from young Sprague Dawley rats to shear stress, VEGF and the combination of the two stimuli. Our study showed that the combined stimulation of shear stress and VEGF resulted in more profound EC oriented differentiation of MSCs in comparison to any individual stimulation. Furthermore, we subjected MSCs to prolonged period of fluid shear stimulation, i.e. 48 hr rather than 24hr, and increased the magnitude of the shear stress from 10 dyn/cm(2) to 15, 20 and 25 dyn/cm(2). We found that without VEGF, the endothelium oriented differentiation of MSCs that was seen following 24hr of shear stimulation was largely abolished if we extended the shear stimulation to 48hr. A similar sharp decrease in MSC differentiation was also observed when the magnitude of the shear stress was increased from 10-15 dyn/cm(2) to 20-25 dyn/cm(2) in 24hr shear stimulation studies. However, with combined VEGF and fluid shear stimulation, most of the endothelial differentiation was retained following an extended period, i.e. at 48 hr, of shear stimulation. Our study demonstrates that chemical and mechanical stimulations work together in determining MSC differentiation dynamics.