Renal clearance is an important route of drug elimination from the bloodstream, mainly facilitated by the proximal tubule, which renders proximal tubule epithelial cells prone to drug-induced kidney injury. Mimicking the in vivo environment by including extracellular matrix (ECM) components, three-dimensional (3D) architectural features, a heterogeneous cellular composition and incorporating fluid shear stress in an in vitro kidney model could improve prediction of injury after drug exposures. These features need to be taken into consideration when trying to develop new in vitro models. The complex renal ECM, recently reviewed in (van Genderen et al. 2018), is in constant remodeling, especially in the transition of healthy to disease state, such as fibrosis. As fibrosis affect the different compartments of the kidney, a comprehensive analysis of the renal ECM is crucial to study the pathophysiology of the disease and its specific biomarkers (Bülow and Boor 2019). As stated before, shear stress triggers mechanosensitive pathways via microvilli, cilia, and the glycocalyx. Understanding how these structures coordinate with each other in response to flow will broaden our knowledge and help identify new molecular targets of diseases (Raghavan and Weisz 2016). Combining these features in a 3D model that includes tubule curvature (Yu et al. 2018) will allow for a better cell polarization and enhanced expression of cell markers.
koeppen and stanton renal physiology pdf download
2ff7e9595c
Comments