Renal reabsorption in 3D vascularized proximal tubule models. 2019

Neil Y C Lin, and Kimberly A Homan, and Sanlin S Robinson, and David B Kolesky, and Nathan Duarte, and Annie Moisan, and Jennifer A Lewis
Wyss Institute for Biologically Inspired Engineering, Harvard University, Boston, MA 02115.

Three-dimensional renal tissues that emulate the cellular composition, geometry, and function of native kidney tissue would enable fundamental studies of filtration and reabsorption. Here, we have created 3D vascularized proximal tubule models composed of adjacent conduits that are lined with confluent epithelium and endothelium, embedded in a permeable ECM, and independently addressed using a closed-loop perfusion system to investigate renal reabsorption. Our 3D kidney tissue allows for coculture of proximal tubule epithelium and vascular endothelium that exhibits active reabsorption via tubular-vascular exchange of solutes akin to native kidney tissue. Using this model, both albumin uptake and glucose reabsorption are quantified as a function of time. Epithelium-endothelium cross-talk is further studied by exposing proximal tubule cells to hyperglycemic conditions and monitoring endothelial cell dysfunction. This diseased state can be rescued by administering a glucose transport inhibitor. Our 3D kidney tissue provides a platform for in vitro studies of kidney function, disease modeling, and pharmacology.

UI MeSH Term Description Entries
D007687 Kidney Tubules, Proximal The renal tubule portion that extends from the BOWMAN CAPSULE in the KIDNEY CORTEX into the KIDNEY MEDULLA. The proximal tubule consists of a convoluted proximal segment in the cortex, and a distal straight segment descending into the medulla where it forms the U-shaped LOOP OF HENLE. Proximal Kidney Tubule,Proximal Renal Tubule,Kidney Tubule, Proximal,Proximal Kidney Tubules,Proximal Renal Tubules,Renal Tubule, Proximal,Renal Tubules, Proximal,Tubule, Proximal Kidney,Tubule, Proximal Renal,Tubules, Proximal Kidney,Tubules, Proximal Renal
D008854 Microscopy, Electron Microscopy using an electron beam, instead of light, to visualize the sample, thereby allowing much greater magnification. The interactions of ELECTRONS with specimens are used to provide information about the fine structure of that specimen. In TRANSMISSION ELECTRON MICROSCOPY the reactions of the electrons that are transmitted through the specimen are imaged. In SCANNING ELECTRON MICROSCOPY an electron beam falls at a non-normal angle on the specimen and the image is derived from the reactions occurring above the plane of the specimen. Electron Microscopy
D008954 Models, Biological Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment. Biological Model,Biological Models,Model, Biological,Models, Biologic,Biologic Model,Biologic Models,Model, Biologic
D005947 Glucose A primary source of energy for living organisms. It is naturally occurring and is found in fruits and other parts of plants in its free state. It is used therapeutically in fluid and nutrient replacement. Dextrose,Anhydrous Dextrose,D-Glucose,Glucose Monohydrate,Glucose, (DL)-Isomer,Glucose, (alpha-D)-Isomer,Glucose, (beta-D)-Isomer,D Glucose,Dextrose, Anhydrous,Monohydrate, Glucose
D006801 Humans Members of the species Homo sapiens. Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000418 Albumins Water-soluble proteins found in egg whites, blood, lymph, and other tissues and fluids. They coagulate upon heating. Albumin
D021621 Imaging, Three-Dimensional The process of generating three-dimensional images by electronic, photographic, or other methods. For example, three-dimensional images can be generated by assembling multiple tomographic images with the aid of a computer, while photographic 3-D images (HOLOGRAPHY) can be made by exposing film to the interference pattern created when two laser light sources shine on an object. Computer-Assisted Three-Dimensional Imaging,Imaging, Three-Dimensional, Computer Assisted,3-D Image,3-D Imaging,Computer-Generated 3D Imaging,Three-Dimensional Image,Three-Dimensional Imaging, Computer Generated,3 D Image,3 D Imaging,3-D Images,3-D Imagings,3D Imaging, Computer-Generated,3D Imagings, Computer-Generated,Computer Assisted Three Dimensional Imaging,Computer Generated 3D Imaging,Computer-Assisted Three-Dimensional Imagings,Computer-Generated 3D Imagings,Image, 3-D,Image, Three-Dimensional,Images, 3-D,Images, Three-Dimensional,Imaging, 3-D,Imaging, Computer-Assisted Three-Dimensional,Imaging, Computer-Generated 3D,Imaging, Three Dimensional,Imagings, 3-D,Imagings, Computer-Assisted Three-Dimensional,Imagings, Computer-Generated 3D,Imagings, Three-Dimensional,Three Dimensional Image,Three Dimensional Imaging, Computer Generated,Three-Dimensional Images,Three-Dimensional Imaging,Three-Dimensional Imaging, Computer-Assisted,Three-Dimensional Imagings,Three-Dimensional Imagings, Computer-Assisted
D065608 Renal Reabsorption The reuptake of water, ELECTROLYTES, and other substances by the KIDNEY to the blood supply. Renal Absorption,Tubule Reabsorption,Absorption, Renal,Reabsorption, Renal,Reabsorption, Tubule

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