Apical medium flowiInfluences the morphology and physiology of human proximal tubular cells in a microphysiological system
Autor:innen
Specioso, Gabriele
Bovard, David
Zanetti, Filippo
Maranzano, Fabio
Merg, Céline
Sandoz, Antonin
Titz, Bjoern
Hoeng, Julia
Autor:in (Körperschaft)
Publikationsdatum
30.09.2022
Typ der Arbeit
Studiengang
Typ
01A - Beitrag in wissenschaftlicher Zeitschrift
Herausgeber:innen
Herausgeber:in (Körperschaft)
Betreuer:in
Übergeordnetes Werk
Bioengineering
Themenheft
DOI der Originalpublikation
Link
Reihe / Serie
Reihennummer
Jahrgang / Band
9
Ausgabe / Nummer
10
Seiten / Dauer
1-17
Patentnummer
Verlag / Herausgebende Institution
MDPI
Verlagsort / Veranstaltungsort
Auflage
Version
Programmiersprache
Abtretungsempfänger:in
Praxispartner:in/Auftraggeber:in
Zusammenfassung
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.
Schlagwörter
Microfluids, Organ-on chip, Micro-physiological systems, Cilia, Kidney
Fachgebiet (DDC)
600 - Technik, Medizin, angewandte Wissenschaften
Veranstaltung
Startdatum der Ausstellung
Enddatum der Ausstellung
Startdatum der Konferenz
Enddatum der Konferenz
Datum der letzten Prüfung
ISBN
ISSN
1097-0290
0006-3592
0006-3592
Sprache
Englisch
Während FHNW Zugehörigkeit erstellt
Ja
Zukunftsfelder FHNW
Publikationsstatus
Veröffentlicht
Begutachtung
Peer-Review der ganzen Publikation
Open Access-Status
Gold
Lizenz
Zitation
SPECIOSO, Gabriele, David BOVARD, Filippo ZANETTI, Fabio MARANZANO, Céline MERG, Antonin SANDOZ, Bjoern TITZ, Federico DALCANALE, Julia HOENG, Kasper RENGGLI und Laura SUTER-DICK, 2022. Apical medium flowiInfluences the morphology and physiology of human proximal tubular cells in a microphysiological system. Bioengineering. 30 September 2022. Bd. 9, Nr. 10, S. 1–17. DOI 10.3390/bioengineering9100516. Verfügbar unter: https://doi.org/10.26041/fhnw-4641