Duckworth Lab Publishes Enteroid Paper

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Carrie Duckworth

Drug-induced gastrointestinal (GI) toxicities are the most common category of adverse events both during clinical trials and after drug approval.  There is a growing need to develop complex in vitro models that accurately recapitulate events observed in in vivo experimental models and in humans.  This will enable drug development pipelines to become much shorter, thus reducing the time taken for new compounds to move from ‘bench to bedside’ and reduce the currently necessary number of animals used in experimental research. 

The inside layer of the gut is responsible for absorbing all dietary components whilst preventing the intestinal microbiome from gaining entry into the rest of the body, which would cause unwanted inflammation.  Within the CDSS, the Duckworth lab has established 3D “mini-gut” cultures of the intestine (termed “enteroids”) that recapitulate the inside layer of the gut.  

In an exciting new paper, the Duckworth lab demonstrates that enteroids maintain their region-specific identity in culture and that these different regions should all be considered when assessing drug or diet-induced gastrointestinal toxicity.  There is a complex interplay between the immune system and the inside layer of the gut (termed “epithelium”) which may be modulated by drug interactions with both immune and epithelial cellular compartments.  The Duckworth lab has generated co-culture models between bone marrow-derived dendritic cells (BMDC) and enteroid cultures to explore this interaction.  NF-κB2 signalling was shown to be important in regulating how epithelial cells respond to inflammatory stimuli secreted from BMDC.  

NF-κB signalling is modulated by many different classes of drug and therefore this signalling pathway now warrants further exploration in epithelial cells to determine whether it is important in regulating patient-specific responses to treatments and whether it can be manipulated therapeutically to ameliorate gastrointestinal toxicity.

Click here to read the paper.

 

For more publications from CDSS scientists and their collaborators, please visit our Publications pages.