Modelling and Prevention of Acute Kidney Injury through Ischemia and Reperfusion in a Combined Human Renal Proximal Tubule/Blood Vessel-on-a-Chip.
AKI
AKI and ICU nephrology
basic science
coculture
in vitro
kidney-on-a-chip
prevention of renal ischemia damage
proximal tubule
renal ischemia
Journal
Kidney360
ISSN: 2641-7650
Titre abrégé: Kidney360
Pays: United States
ID NLM: 101766381
Informations de publication
Date de publication:
24 02 2022
24 02 2022
Historique:
received:
01
06
2021
accepted:
29
10
2021
entrez:
4
4
2022
pubmed:
5
4
2022
medline:
8
4
2022
Statut:
epublish
Résumé
Renal ischemia/reperfusion injury (rIRI) is one of the major causes of AKI. Although animal models are suitable for investigating systemic symptoms of AKI, they are limited in translatability. Human We advanced the current renal proximal tubule-on-a-chip model to a coculture model with a perfused endothelial vessel separated by an extracellular matrix. The coculture was characterized for its three-dimensional structure, protein expression, and response to nephrotoxins. Then, rIRI was captured through control of oxygen levels, nutrient availability, and perfusion flow settings. Injury was quantified through morphologic assessment, caspase-3/7 activation, and cell viability. The combination of low oxygen, reduced glucose, and interrupted flow was potent to disturb the proximal tubules. This effect was strongly amplified upon reperfusion. Endothelial vessels were less sensitive to the ischemia-reperfusion parameters. Adenosine treatment showed a protective effect on the disruption of the epithelium and on the caspase-3/7 activation. A human
Sections du résumé
Background
Renal ischemia/reperfusion injury (rIRI) is one of the major causes of AKI. Although animal models are suitable for investigating systemic symptoms of AKI, they are limited in translatability. Human
Methods
We advanced the current renal proximal tubule-on-a-chip model to a coculture model with a perfused endothelial vessel separated by an extracellular matrix. The coculture was characterized for its three-dimensional structure, protein expression, and response to nephrotoxins. Then, rIRI was captured through control of oxygen levels, nutrient availability, and perfusion flow settings. Injury was quantified through morphologic assessment, caspase-3/7 activation, and cell viability.
Results
The combination of low oxygen, reduced glucose, and interrupted flow was potent to disturb the proximal tubules. This effect was strongly amplified upon reperfusion. Endothelial vessels were less sensitive to the ischemia-reperfusion parameters. Adenosine treatment showed a protective effect on the disruption of the epithelium and on the caspase-3/7 activation.
Conclusions
A human
Identifiants
pubmed: 35373131
doi: 10.34067/KID.0003622021
pii: 02200512-202202000-00008
pmc: PMC8967632
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
217-231Commentaires et corrections
Type : CommentIn
Informations de copyright
Copyright © 2022 by the American Society of Nephrology.
Déclaration de conflit d'intérêts
L. Gijzen, H.L. Lanz, L.M. Tool, R. van Vught, M.K. Vormann, and P. Vulto are employees of MIMETAS BV, The Netherlands, which is marketing the OrganoPlate. T. Hankemeier and P. Vulto are shareholders of that same company. OrganoPlate is a trademark of MIMETAS BV. All remaining authors have nothing to disclose.
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