Apical medium flowiInfluences the morphology and physiology of human proximal tubular cells in a microphysiological system
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Authors
Specioso, Gabriele
Bovard, David
Zanetti, Filippo
Maranzano, Fabio
Merg, Céline
Sandoz, Antonin
Titz, Bjoern
Hoeng, Julia
Author (Corporation)
Publication date
30.09.2022
Typ of student thesis
Course of study
Collections
Type
01A - Journal article
Editors
Editor (Corporation)
Supervisor
Parent work
Bioengineering
Special issue
DOI of the original publication
Link
Series
Series number
Volume
9
Issue / Number
10
Pages / Duration
1-17
Patent number
Publisher / Publishing institution
MDPI
Place of publication / Event location
Edition
Version
Programming language
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Practice partner / Client
Abstract
There is a lack of physiologically relevant in vitro human kidney models for disease modelling and detecting drug-induced effects given the limited choice of cells and difficulty implementing quasi-physiological culture conditions. We investigated the influence of fluid shear stress on primary human renal proximal tubule epithelial cells (RPTECs) cultured in the micro-physiological Vitrofluid device. This system houses cells seeded on semipermeable membranes and can be connected to a regulable pump that enables controlled, unidirectional flow. After 7 days in culture, RPTECs maintained physiological characteristics such as barrier integrity, protein uptake ability, and expression of specific transporters (e.g., aquaporin-1). Exposure to constant apical side flow did not cause cytotoxicity, cell detachment, or intracellular reactive oxygen species accumulation. However, unidirectional flow profoundly affected cell morphology and led to primary cilia lengthening and alignment in the flow direction. The dynamic conditions also reduced cell proliferation, altered plasma membrane leakiness, increased cytokine secretion, and repressed histone deacetylase 6 and kidney injury molecule 1 expression. Cells under flow also remained susceptible to colistin-induced toxicity. Collectively, the results suggest that dynamic culture conditions in the Vitrofluid system promote a more differentiated phenotype in primary human RPTECs and represent an improved in vitro kidney model.
Keywords
Microfluids, Organ-on chip, Micro-physiological systems, Cilia, Kidney
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ISBN
ISSN
1097-0290
0006-3592
0006-3592
Language
English
Created during FHNW affiliation
Yes
Strategic action fields FHNW
Publication status
Published
Review
Peer review of the complete publication
Open access category
Gold
License
Citation
Specioso, G., Bovard, D., Zanetti, F., Maranzano, F., Merg, C., Sandoz, A., Titz, B., Dalcanale, F., Hoeng, J., Renggli, K., & Suter-Dick, L. (2022). Apical medium flowiInfluences the morphology and physiology of human proximal tubular cells in a microphysiological system. Bioengineering, 9(10), 1–17. https://doi.org/10.3390/bioengineering9100516