Staff Publications

Staff Publications

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    'Staff publications' is the digital repository of Wageningen University & Research

    'Staff publications' contains references to publications authored by Wageningen University staff from 1976 onward.

    Publications authored by the staff of the Research Institutes are available from 1995 onwards.

    Full text documents are added when available. The database is updated daily and currently holds about 240,000 items, of which 72,000 in open access.

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Record number 550620
Title Development and validation of bioengineered intestinal tubules for translational research aimed at safety and efficacy testing of drugs and nutrients
Author(s) Jochems, Paulus G.M.; Bergenhenegouwen, Jeroen van; Genderen, Anne Metje van; Eis, Sophie T.; Wilod Versprille, Livia J.F.; Wichers, Harry J.; Jeurink, Prescilla V.; Garssen, Johan; Masereeuw, Rosalinde
Source Toxicology in Vitro 60 (2019). - ISSN 0887-2333 - p. 1 - 11.
DOI https://doi.org/10.1016/j.tiv.2019.04.019
Department(s) Food, Health & Consumer Research
VLAG
Publication type Refereed Article in a scientific journal
Publication year 2019
Keyword(s) Caco-2 - In vitro - Microfluidic and screening - Small intestine
Abstract

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.

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