Research
Print page Print page
Switch language
The Capital Region of Denmark - a part of Copenhagen University Hospital
Published

Validation and Optimization of an Ex Vivo Assay of Intestinal Mucosal Biopsies in Crohn's Disease: Reflects Inflammation and Drug Effects

Research output: Contribution to journalJournal articleResearchpeer-review

  1. Protocol: Benefits and harms of remdesivir for COVID-19 in adults: A systematic review with meta-analysis

    Research output: Contribution to journalReviewResearchpeer-review

  2. Carotid plaque thickness is increased in chronic kidney disease and associated with carotid and coronary calcification

    Research output: Contribution to journalJournal articleResearchpeer-review

  3. Investigating the inflammation marker neutrophil-to-lymphocyte ratio in Danish blood donors with restless legs syndrome

    Research output: Contribution to journalJournal articleResearchpeer-review

View graph of relations

Crohn's disease (CD) is a chronic illness demanding better therapeutics. The marketed biologics only benefit some patients or elicit diminishing effect over time. To complement the known methods in drug development and to obtain patient specific drug responses, we optimized and validated a known human explant method to test drug candidates and pathophysiological conditions in CD intestinal biopsies. Mucosal biopsies from 27 CD patients and 6 healthy individuals were collected to validate an explant assay test where the polarized tissue was cultured on a novel metal mesh disk, slightly immersed in medium imitating an air-liquid interphase. After culture in high oxygen for 24 hours with or without biological treatment in the medium, biopsy integrity and penetration of antibodies was measured by immunohistochemistry (IHC). Nine cytokines were quantified in the conditioned medium as a read-out for degree of inflammation in individual biopsies and used to evaluate treatment efficacy. The biopsies were well-preserved, showing few structural changes. IHC revealed tissue penetration of antibodies demonstrating ability to test therapeutic antibodies. The cytokine release to the medium showed that the assay can distinguish between inflammation states and then validate the known effect of two treatment biologics confirmed by a detection panel of five specific cytokines. Our data also suggest that the assay would be able to indicate which patients are responders to anti-TNF-α therapeutics, and which are non-responders. This study demonstrates this version of an ex vivo culture as a valid and robust assay to assess inflammation in mucosal biopsies and test of the efficacy of novel drug candidates and current treatments on individual patients-potentially for a personalized medicine approach.

Original languageEnglish
JournalP L o S One
Volume11
Issue number5
Pages (from-to)e0155335
ISSN1932-6203
DOIs
Publication statusPublished - 2016

    Research areas

  • Journal Article

ID: 48377876