Reconstructing the Human Renal Vascular-Tubular Unit In Vitro.

Autor: Rayner SG; Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98105, USA.; Department of Pulmonary, Critical Care, and Sleep Medicine, University of Washington, Seattle, WA, 98195, USA., Phong KT; Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98105, USA., Xue J; Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98105, USA., Lih D; Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98105, USA., Shankland SJ; Department of Medicine, University of Washington, Seattle, WA, 98195, USA.; Kidney Research Institute, Seattle, WA, 98104, USA., Kelly EJ; Kidney Research Institute, Seattle, WA, 98104, USA.; Institute for Stem Cell and Regenerative Medicine, Seattle, WA, 98195, USA.; Department of Pharmaceutics, University of Washington, Seattle, WA, 98195, USA., Himmelfarb J; Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98105, USA.; Department of Medicine, University of Washington, Seattle, WA, 98195, USA.; Kidney Research Institute, Seattle, WA, 98104, USA., Zheng Y; Department of Bioengineering, University of Washington, 3720 15th Ave NE, Seattle, WA, 98105, USA.; Kidney Research Institute, Seattle, WA, 98104, USA.; Institute for Stem Cell and Regenerative Medicine, Seattle, WA, 98195, USA.
Jazyk: angličtina
Zdroj: Advanced healthcare materials [Adv Healthc Mater] 2018 Dec; Vol. 7 (23), pp. e1801120. Date of Electronic Publication: 2018 Oct 31.
DOI: 10.1002/adhm.201801120
Abstrakt: 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.
(© 2018 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)
Databáze: MEDLINE
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