Dataset Information

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.

SUBMITTER: Ligresti G

PROVIDER: S-EPMC4978055 | biostudies-literature | 2016 Aug

REPOSITORIES: biostudies-literature

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Publications

A Novel Three-Dimensional Human Peritubular Microvascular System.

Ligresti Giovanni G Nagao Ryan J RJ Xue Jun J Choi Yoon Jung YJ Xu Jin J Ren Shuyu S Aburatani Takahide T Anderson Susan K SK MacDonald James W JW Bammler Theo K TK Schwartz Stephen M SM Muczynski Kimberly A KA Duffield Jeremy S JS Himmelfarb Jonathan J Zheng Ying Y

Journal of the American Society of Nephrology : JASN 20151211 8

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 microphysiol ...[more]

PMID: 26657868

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Project description:Tissue engineering is an essential component of developing effective regenerative therapies. In this study, we introduce a promising method to create scaffold-free three-dimensional (3D) tissue engineered multilayered microstructures from cultured cells using the "3D tissue fabrication system" (Regenova®; Cyfuse, Tokyo, Japan). This technique utilizes the adhesive nature of cells. When cells are cultured in nonadhesive wells, they tend to aggregate and form a spheroidal structure. The advantage of this approach is that cellular components can be mixed into one spheroid, thereby promoting the formation of extracellular matrices, such as collagen and elastin. This system enables one to create a predesigned 3D structure composed of cultured cells. We found that the advantages of this system to be (1) the length, size, and shape of the structure that were designable and highly reproducible because of the computer controlled robotics system, (2) the graftable structure could be created within a reasonable period (8 days), and (3) the constructed tissue did not contain any foreign material, which may avoid the potential issues of contamination, biotoxicity, and allergy. The utilization of this robotic system enabled the creation of a 3D multilayered microstructure made of cell-based spheres with a satisfactory mechanical properties and abundant extracellular matrix during a short period of time. These results suggest that this new technology will represent a promising, attractive, and practical strategy in the field of tissue engineering. Impact statement The utilization of the "three dimensional tissue fabrication system" enabled the creation of a three-dimensional (3D) multilayered microstructure made of cell-based spheres with a satisfactory mechanical properties and abundant extracellular matrix during a short period of time. These results suggest that this new technology will represent a promising, attractive, and practical strategy in the field of tissue engineering.

Dataset Information

A Novel Three-Dimensional Human Peritubular Microvascular System.

Publications

A Novel Three-Dimensional Human Peritubular Microvascular System.

Similar Datasets

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