| Autor: |
Specioso G; School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, Switzerland., Bovard D; Philip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland., Zanetti F; Philip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland., Maranzano F; Philip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland., Merg C; Philip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland., Sandoz A; Philip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland., Titz B; Philip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland., Dalcanale F; School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, Switzerland., Hoeng J; Philip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland., Renggli K; Philip Morris International (PMI) R&D, Philip Morris Products S.A., Quai Jeanrenaud 5, 2000 Neuchatel, Switzerland., Suter-Dick L; School of Life Sciences, University of Applied Sciences and Arts Northwestern Switzerland, 4132 Muttenz, Switzerland.; Swiss Centre for Applied Human Toxicology (SCAHT), 4056 Basel, Switzerland. |
| Abstrakt: |
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. |
