Renal reabsorption in 3D vascularized proximal tubule models
| Autor: | Nathan Duarte, Sanlin S. Robinson, Kimberly A. Homan, Jennifer A. Lewis, David B. Kolesky, Neil Y. C. Lin, Annie Moisan |
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| Rok vydání: | 2019 |
| Předmět: |
vasculature
Endothelium Renal function 02 engineering and technology Models Biological Kidney Tubules Proximal 03 medical and health sciences Imaging Three-Dimensional Engineering Albumins proximal tubule medicine Humans reabsorption 030304 developmental biology 0303 health sciences Kidney Multidisciplinary Reabsorption Chemistry Glucose transporter Renal Reabsorption kidney tissue 021001 nanoscience & nanotechnology Epithelium 3. Good health Cell biology Renal glucose reabsorption Microscopy Electron medicine.anatomical_structure Glucose Physical Sciences 0210 nano-technology bioprinting |
| Zdroj: | Proceedings of the National Academy of Sciences of the United States of America |
| ISSN: | 1091-6490 |
| Popis: | Significance Current kidney-on-chip models lack the 3D geometry, complexity, and functionality vital for recapitulating in vivo renal tissue. We report the fabrication and perfusion of 3D vascularized proximal tubules embedded within an engineered ECM that exhibit active reabsorption of solutes via tubular–vascular exchange. Using this model, we quantified albumin and glucose reabsorption over time. We also studied hyperglycemic effects in the absence and presence of a glucose transport inhibitor. Our 3D kidney tissue provides a platform for in vitro studies of kidney function, disease modeling, and pharmacology. 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. |
| Databáze: | OpenAIRE |
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