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Titel: Inflammatory bowel disease addressed by Caco-2 and monocyte-derived macrophages : an opportunity for an in vitro drug screening assay
VerfasserIn: Schnur, Sabrina
Wahl, Vanessa
Metz, Julia K.
Gillmann, Jessica
Hans, Fabian
Rotermund, Katharina
Zäh, Ralf-Kilian
Brück, Dietmar A.
Schneider, Marc UdsID
Hittinger, Marius
Sprache: Englisch
In:
Titel: In vitro models
Bandnummer: 1
Heft: 4-5
Seiten: 365-383
Verlag/Plattform: Springer Nature
Erscheinungsjahr: 2022
Freie Schlagwörter: Chronic infammation of GI-tract
Cell-based co-culture
IVIVC
Drug testing
Efcacy outcome pathways
DDC-Sachgruppe: 500 Naturwissenschaften
Dokumenttyp: Journalartikel / Zeitschriftenartikel
Abstract: Infammatory bowel disease (IBD) is a widespread disease, afecting a growing demographic. The treatment of chronic infammation located in the GI-tract is dependent on the severity; therefore, the IBD treatment pyramid is commonly applied. Animal experimentation plays a key role for novel IBD drug development; nevertheless, it is ethically questionable and limited in its throughput. Reliable and valid in vitro assays ofer the opportunity to overcome these limitations. We combined Caco-2 with monocyte-derived macrophages and exposed them to known drugs, targeting an in vitro-in vivo correlation (IVIVC) with a focus on the severity level and its related drug candidate. This co-culture assay addresses namely the intestinal barrier and the immune response in IBD. The drug efcacy was analyzed by an LPS-infammation of the co-culture and drug exposure according to the IBD treatment pyramid. Efcacy was defned as the range between LPS control (0%) and untreated co-culture (100%) independent of the investigated read-out (TEER, Papp, cytokine release: IL-6, IL-8, IL-10, TNF-α). The release of IL-6, IL-8, and TNF-α was identifed as an appropriate readout for a fast drug screening (“yes–no response”). TEER showed a remarkable IVIVC correlation to the human treatment pyramid (5-ASA, Prednisolone, 6-mercaptopurine, and infiximab) with an R2 of 0.68. Similar to the description of an adverse outcome pathway (AOP) framework, we advocate establishing an “Efcacy Outcome Pathways (EOPs)” framework for drug efcacy assays. The in vitro assay ofers an easy and scalable method for IBD drug screening with a focus on human data, which requires further validation.
DOI der Erstveröffentlichung: 10.1007/s44164-022-00035-8
URL der Erstveröffentlichung: https://link.springer.com/article/10.1007/s44164-022-00035-8
Link zu diesem Datensatz: urn:nbn:de:bsz:291--ds-388036
hdl:20.500.11880/34964
http://dx.doi.org/10.22028/D291-38803
ISSN: 2731-3441
Datum des Eintrags: 23-Jan-2023
Bezeichnung des in Beziehung stehenden Objekts: Supplementary Information
In Beziehung stehendes Objekt: https://static-content.springer.com/esm/art%3A10.1007%2Fs44164-022-00035-8/MediaObjects/44164_2022_35_MOESM1_ESM.docx
Fakultät: NT - Naturwissenschaftlich- Technische Fakultät
Fachrichtung: NT - Pharmazie
Professur: NT - Prof. Dr. Marc Schneider
Sammlung:SciDok - Der Wissenschaftsserver der Universität des Saarlandes



Diese Ressource wurde unter folgender Copyright-Bestimmung veröffentlicht: Lizenz von Creative Commons Creative Commons