Flow-adapted vascular systems: mimicking the vascular network to predict clinical response to radiation

The endothelium lines the vascular network that is distributed in every tissue. Hence, it pervades the entire body and is exposed to radiation when faced with a radiation field, irrespective of whether the radiation emanates from a site-directed or whole-body radiation protocol. The endothelium mediates systemic and local inflammatory reactions and plays a functional role in orchestrating an acute or delayed radiation response. Considerable attempts were made to gain insights into the endothelial response to radiation. The in vitro models used thus far for mechanistic studies, however, have failed to mimic the in vivo environment. This is because the endothelial cells used in radiation studies, have been largely statically cultured cells that are not under the stimulus of blood flow as would occur in vivo. The effect of shear stress on the physiological function of the endothelium and associated mechanotransduction signaling must be considered, in order to evaluate the effects of exposure to radiation and eventually to translate findings to health and disease. This chapter highlights the significance of factoring in context-specific shear forces relevant to the site (vascular bed) and origins, and context-specific radiation quality, dose, dose-rate, and fractionation in fabrication of in vitro platforms to assess the endothelial response to radiation.