Effects of Mechanical and Chemical Stimuli on Differentiation of Human Adipose-Derived Stem Cells into Endothelial Cells

Abstract

It has been hypothesized that application of the micromechanical environment that target cells experience in vivo enhances functionality of differentiated cells. Vascular endothelial cells, functioning at the interface of the blood-vessel wall, are vital to the performance of the cardiovascular system. They are subject to shear and tensile stresses induced by blood flow and pressure, respectively. This study investigated effects of shear/tensile stresses on endothelial differentiation of adipose-derived mesenchymal stem cells (ASCs) utilizing a custom-made bioreactor capable of applying both shear and tensile stresses. The loading values of 10% cyclic stretch, 0-2.5 dyn/cm² cyclic shear stress, and combined loadings were used. To examine the extent of mechanical and chemical stimuli in acquisition of endothelial characteristics by ASCs, the expression of three major endothelial genes were quantified when ASCs were treated by three loading regimes and endothelial growth factor for three different durations (1, 2, and 7 days). In general, cyclic stretch decreased expression of FLK-1 and vWF, while cyclic shear elevated expression levels. The combined loading regime had minor effects on the expression of the two markers. All types of loadings significantly enhanced the expression level of VE-cadherin with the most prominent increase by combined loading. It was concluded that applying different loading regimes assists in adjusting the expression level of endothelial markers to achieve functional endothelial cells for cardiovascular engineering.