Here we expand upon that work using a novel shear stress device developed in our laboratory. A unique feature of this device is that cells are cultured in a standard tissue culture treated 6-well plate, thereby avoiding any problems related to surface attachment. Exposing adherent vascular derivatives of hESCs at different developmental stages to shear (0 to 15 dyne/cm2) had a dramatic effect on derivation and maturation. Using this high-throughput system, embryonic derivatives were easily compared to various mature vascular cell arrangement and angiogenesis potential under shear stress conditions. Next, we considered the shear response of hESCs cultured in the three-dimensional environment (3D) of a hydrogel. A precise channel in the hydrogel was created by photocrosslinking (hyaluronic acid) or setting (collagen) the hydrogel around a rod in a specially designed chamber. Once the rod was removed, medium flow through the channel exposed cells to defined shear stress, the value of which was easily calculated from Hagen-Poiseuille relation. Both encapsulation of cells within the hydrogel, as well as seeding cells into already formed channel, were considered. Finally, a microchannel microfluidic device was designed and tested to study the response of individual cells to shear, electrical stimuli, and cytokine signaling.