Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System
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...
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MDPI AG
2022-09-01
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| Series: | Bioengineering |
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| Online Access: | https://www.mdpi.com/2306-5354/9/10/516 |
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| author | Gabriele Specioso David Bovard Filippo Zanetti Fabio Maranzano Céline Merg Antonin Sandoz Bjoern Titz Federico Dalcanale Julia Hoeng Kasper Renggli Laura Suter-Dick |
| author_facet | Gabriele Specioso David Bovard Filippo Zanetti Fabio Maranzano Céline Merg Antonin Sandoz Bjoern Titz Federico Dalcanale Julia Hoeng Kasper Renggli Laura Suter-Dick |
| author_sort | Gabriele Specioso |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-03-09T20:42:00Z |
| format | Article |
| id | doaj.art-9768d7691aea44418f258a4203caa8d7 |
| institution | Directory Open Access Journal |
| issn | 2306-5354 |
| language | English |
| last_indexed | 2024-03-09T20:42:00Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Bioengineering |
| spelling | doaj.art-9768d7691aea44418f258a4203caa8d72023-11-23T22:57:12ZengMDPI AGBioengineering2306-53542022-09-0191051610.3390/bioengineering9100516Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological SystemGabriele Specioso0David Bovard1Filippo Zanetti2Fabio Maranzano3Céline Merg4Antonin Sandoz5Bjoern Titz6Federico Dalcanale7Julia Hoeng8Kasper Renggli9Laura Suter-Dick10School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, SwitzerlandPhilip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, SwitzerlandPhilip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, SwitzerlandPhilip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, SwitzerlandPhilip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, SwitzerlandPhilip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, SwitzerlandPhilip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, SwitzerlandSchool of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, SwitzerlandPhilip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, SwitzerlandPhilip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, SwitzerlandSchool of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, SwitzerlandThere 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.https://www.mdpi.com/2306-5354/9/10/516microfluidicsorgan-on-chipmicro-physiological systemsciliakidney |
| spellingShingle | Gabriele Specioso David Bovard Filippo Zanetti Fabio Maranzano Céline Merg Antonin Sandoz Bjoern Titz Federico Dalcanale Julia Hoeng Kasper Renggli Laura Suter-Dick Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System Bioengineering microfluidics organ-on-chip micro-physiological systems cilia kidney |
| title | Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System |
| title_full | Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System |
| title_fullStr | Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System |
| title_full_unstemmed | Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System |
| title_short | Apical Medium Flow Influences the Morphology and Physiology of Human Proximal Tubular Cells in a Microphysiological System |
| title_sort | apical medium flow influences the morphology and physiology of human proximal tubular cells in a microphysiological system |
| topic | microfluidics organ-on-chip micro-physiological systems cilia kidney |
| url | https://www.mdpi.com/2306-5354/9/10/516 |
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