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Reconstructing the Human Renal Vascular–Tubular Unit In Vitro
Author(s) -
Rayner Samuel G.,
Phong Kiet T.,
Xue Jun,
Lih Daniel,
Shankland Stuart J.,
Kelly Edward J.,
Himmelfarb Jonathan,
Zheng Ying
Publication year - 2018
Publication title -
advanced healthcare materials
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.288
H-Index - 90
eISSN - 2192-2659
pISSN - 2192-2640
DOI - 10.1002/adhm.201801120
Subject(s) - kidney , basement membrane , reabsorption , interface (matter) , kidney disease , matrix (chemical analysis) , biomedical engineering , extracellular matrix , organ on a chip , renal physiology , microbiology and biotechnology , chemistry , computer science , materials science , nanotechnology , medicine , biology , biochemistry , microfluidics , pulmonary surfactant , gibbs isotherm , chromatography
Engineered human kidney‐on‐a‐chip platforms show tremendous promise for disease modeling and drug screening. Outstanding challenges exist, however, in reconstructing the complex architecture, cellular make‐up, and matrix composition necessary for the proper modeling of kidney function. Herein, the first fully tunable human kidney‐on‐a‐chip platform is reported that allows the reconstruction of the native architecture of the renal endothelial–epithelial exchange interface using entirely cell‐remodelable matrix and patient‐derived kidney cells. This platform consists of a double‐layer human renal vascular–tubular unit (hRVTU) enabled by a thin collagen membrane that replicates the kidney exchange interface. It is shown that endothelial and epithelial cells lining their respective lumens remodel the membrane in culture into a ≈1 µm thick exchange interface composed of native basement membrane proteins. This interface displays sufficient mechanical integrity for media flow and blood perfusion. As a proof of principle, it is demonstrated that the hRVTU performs kidney‐specific functions including reabsorption of albumin and glucose from the epithelial channel. By incorporating multiple cell populations from single donors, it is demonstrated that the hRVTU may have utility for future precision medicine applications. The success of the system provides new opportunities for the next generation of organ‐on‐a‐chip models.