Patient Derived Colonoids as Drug Testing Platforms-Critical Importance of Oxygen Concentration.

cytokines epithelium inflammatory bowel diseases interleukin 17 organoids oxygen tumor necrosis factor

Journal

Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923

Informations de publication

Date de publication:
2021
Historique:
received: 12 03 2021
accepted: 28 04 2021
entrez: 31 5 2021
pubmed: 1 6 2021
medline: 1 6 2021
Statut: epublish

Résumé

Treatment of inflammatory bowel disease (IBD) is challenging, with a series of available drugs each helping only a fraction of patients. Patients may face time-consuming drug trials while the disease is active, thus there is an unmet need for biomarkers and assays to predict drug effect. It is well known that the intestinal epithelium is an important factor in disease pathogenesis, exhibiting physical, biochemical and immunologic driven barrier dysfunctions. One promising test system to study effects of existing or emerging IBD treatments targeting intestinal epithelial cells (IECs) is intestinal organoids ("mini-guts"). However, the fact that healthy intestinal epithelium is in a physiologically hypoxic state has largely been neglected, and studies with intestinal organoids are mainly performed at oxygen concentration of 20%. We hypothesized that lowering the incubator oxygen level from 20% to 2% would recapitulate better the

Identifiants

pubmed: 34054553
doi: 10.3389/fphar.2021.679741
pii: 679741
pmc: PMC8156408
doi:

Types de publication

Journal Article

Langues

eng

Pagination

679741

Informations de copyright

Copyright © 2021 Skovdahl, Gopalakrishnan, Svendsen, Granlund, Bakke, Ginbot, Thorsvik, Flatberg, Sporsheim, Ostrop, Mollnes, Sandvik and Bruland.

Déclaration de conflit d'intérêts

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

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Auteurs

Helene Kolstad Skovdahl (HK)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.

Shreya Gopalakrishnan (S)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.

Tarjei Dahl Svendsen (TD)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.

Atle van Beelen Granlund (AVB)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.

Ingunn Bakke (I)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Clinic of Laboratory Medicine, St. Olav's University Hospital, Trondheim, Norway.

Zekarias G Ginbot (ZG)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.

Silje Thorsvik (S)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway.

Arnar Flatberg (A)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Central Administration, St Olavs Hospital, The University Hospital in Trondheim, Trondheim, Norway.

Bjørnar Sporsheim (B)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Central Administration, St Olavs Hospital, The University Hospital in Trondheim, Trondheim, Norway.

Jenny Ostrop (J)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.

Tom Eirik Mollnes (TE)

Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Research Laboratory, Nordland Hospital, Bodø, Norway.
K.G. Jebsen Thrombosis Research and Expertise Centre, Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.
Department of Immunology, Oslo University Hospital and University of Oslo, Oslo, Norway.

Arne Kristian Sandvik (AK)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Centre of Molecular Inflammation Research (CEMIR), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Department of Gastroenterology and Hepatology, Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway.

Torunn Bruland (T)

Department of Clinical and Molecular Medicine (IKOM), Faculty of Medicine and Health Sciences, NTNU- Norwegian University of Science and Technology, Trondheim, Norway.
Clinic of Medicine, St. Olav's University Hospital, Trondheim, Norway.

Classifications MeSH