title: A Novel Three-Dimensional Human Peritubular Microvascular System.
abstract: Human kidney peritubular capillaries are particularly susceptible to injury, resulting in dysregulated angiogenesis, capillary rarefaction and regression, and progressive loss of kidney function. However, little is known about the structure and function of human kidney microvasculature. Here, we isolated, purified, and characterized human kidney peritubular microvascular endothelial cells (HKMECs) and reconstituted a three-dimensional human kidney microvasculature in a flow-directed microphysiologic system. By combining epithelial cell depletion and cell culture in media with high concentrations of vascular endothelial growth factor, we obtained HKMECs of high purity in large quantity. Unlike other endothelial cells, isolated HKMECs depended on high vascular endothelial growth factor concentration for survival and growth and exhibited high tubulogenic but low angiogenic potential. Furthermore, HKMECs had a different transcriptional profile. Under flow, HKMECs formed a thin fenestrated endothelium with a functional permeability barrier. In conclusion, this three-dimensional HKMEC-specific microphysiologic system recapitulates human kidney microvascular structure and function and shows phenotypic characteristics different from those of other microvascular endothelial cells.
authors.affiliation: Departments of Bioengineering, Medicine.
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ligresti
authors.affiliation: Departments of Bioengineering.
authors.forename: Ryan J
authors.initials: RJ
authors.lastname: Nagao
authors.affiliation: Departments of Bioengineering.
authors.forename: Jun
authors.initials: J
authors.lastname: Xue
authors.affiliation: Departments of Bioengineering.
authors.forename: Yoon Jung
authors.initials: YJ
authors.lastname: Choi
authors.affiliation: Departments of Bioengineering.
authors.forename: Jin
authors.initials: J
authors.lastname: Xu
authors.affiliation: Medicine.
authors.forename: Shuyu
authors.initials: S
authors.lastname: Ren
authors.affiliation: Medicine.
authors.forename: Takahide
authors.initials: T
authors.lastname: Aburatani
authors.affiliation: Medicine.
authors.forename: Susan K
authors.initials: SK
authors.lastname: Anderson
authors.affiliation: Environmental and Occupational Health Sciences, and.
authors.forename: James W
authors.initials: JW
authors.lastname: MacDonald
authors.affiliation: Environmental and Occupational Health Sciences, and.
authors.forename: Theo K
authors.initials: TK
authors.lastname: Bammler
authors.affiliation: Pathology.
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Schwartz
authors.affiliation: Medicine.
authors.forename: Kimberly A
authors.initials: KA
authors.lastname: Muczynski
authors.affiliation: Medicine, Kidney Research Institute, and.
authors.forename: Jeremy S
authors.initials: JS
authors.lastname: Duffield
authors.affiliation: Medicine, Kidney Research Institute, and himmej@u.washington.edu yingzy@uw.edu.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Himmelfarb
authors.affiliation: Departments of Bioengineering, Institute for Stem Cell and Regenerative Medicine, University of Washington, Seattle, Washington himmej@u.washington.edu yingzy@uw.edu.
authors.forename: Ying
authors.initials: Y
authors.lastname: Zheng
mesh_terms: D002196:Capillaries / Q000166:cytology*; D002478:Cells, Cultured; D018450:Disease Progression; D042783:Endothelial Cells; D006801:Humans; D007674:Kidney Diseases / Q000209:etiology; D007684:Kidney Tubules / Q000166:cytology*
keywords: angiogenesis; endothelial cells; fenestrae; kidney; microphysiological system; peritubular microvessels