{Mesenchymal stem cells (MSCs) may benefit vascular cell-based therapies as smooth muscle or endothelial cell substitutes or through paracrine actions to repair, replace, or regenerate vascular tissue. Previous studies have demonstrated that MSCs can adopt traits of smooth muscle cells (SMCs) or endothelial cells (ECs), as well as secrete specific factors that tune signaling and material properties in the local environment. Few studies have investigated the cell signaling response of MSCs to mechanical forces present in the vasculature: specifically, shear stress due to blood flow and cyclic strain due to pulsatile blood flow. Thus, the central objective of this dissertation was to determine the signaling responses of MSCs to vascular-relevant applied physical forces, in comparison with that of differentiated vascular cells. Vascular-relevant mechanosignaling of MSCs was assessed through two comparisons: (1) MSC and SMC responses to applied cyclic strain and (2) MSC and EC responses to applied fluid shear stress. MSCs and SMCs were seeded on fibronectin-coated silicone and subjected in vitro to cyclic strain (10%, 1 Hz) or parallel static culture using a custom-built equibiaxial cyclic strain device. Gene expression analysis of 84 signal transduction molecules demonstrated both cell types respond with significant (p < 0.05