Development and validation of bioengineered intestinal tubules for translational research aimed at safety and efficacy testing of drugs and nutrients.

Currently used intestinal cell models have limited translational value, therefore, development of novel in vitro intestinal models that recapitulate the human in vivo setting more closely are of interest. Here, an advanced intestinal model was developed by the incorporation of physiological parameters, such as extracellular matrix (ECM) elements and shear stress, to cultured Caco-2 cells in a 3-dimensional environment. Caco-2 cells grown on ECM-coated hollow fiber membranes (HFM) under physiological shear stress show an improved phenotype, as demonstrated by the presence of enterocytes, goblet, Paneth, enteroendocrine and stem cells. Additionally, this model showed signs of an improved morphology due to the appearance of villi-like structures. Similar to epithelial cells grown on Transwells™, the current model remains easy to use, cost efficient and allows apical and basolateral access. The bioengineered intestinal tubule was validated by exposure to Clostridium difficile toxin A, the leading cause of healthcare-associated diarrhea. The loss of the tight junction network was supported by an increase in inulin-FITC leakage and the number of goblet cells increased, in agreement with clinical findings. In addition to toxicity screening, the bioengineered intestinal tubules are considered useful for drug and nutrient safety and efficacy testing.

Proceeding of the 9th Alcohol Hangover Research Group Meeting.

BACKGROUND: Alcohol hangover is a common occurrence among individuals who have experienced an episode of heavy alcohol consumption the previous night. Until now defined as the general feeling of misery that develops once the Blood Alcohol Concentration approaches zero. Despite its prevalence and several related adverse consequences, insufficient research has been conducted with regards to this matter and further understanding of the pathology of alcohol hangover is necessary. During the 9th Alcohol Hangover Research Group meeting, held on April 29th 2017, Utrecht, The Netherlands, numerous aspects of alcohol hangover were presented and many advances with regards to determinants, biological and cognitive consequences and potential treatment have been presented. CONCLUSION: Precisely, a definition of alcohol hangover has been established and wider understandings of biological and cognitive effects, alcohol metabolism, immune functioning and potential treatment of alcohol hangover were presented and discussed. Further research and development are necessary to attain a wider understanding of the pathology of alcohol hangover.