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

Paulus G.M. Jochems, Jeroen van Bergenhenegouwen, Anne Metje van Genderen, Sophie T. Eis, Livia J.F. Wilod Versprille, Harry J. Wichers, Prescilla V. Jeurink, Johan Garssen, Rosalinde Masereeuw

Research output: Contribution to journalArticleAcademicpeer-review

1 Citation (Scopus)

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.

LanguageEnglish
Pages1-11
JournalToxicology in Vitro
Volume60
DOIs
Publication statusPublished - Oct 2019

Fingerprint

Goblet Cells
Translational Medical Research
Caco-2 Cells
Nutrients
Extracellular Matrix
Paneth Cells
Enteroendocrine Cells
Safety
Food
Enterocytes
Tight Junctions
Testing
Pharmaceutical Preparations
Cultured Cells
Diarrhea
Stem Cells
Epithelial Cells
Shear stress
Delivery of Health Care
Phenotype

Keywords

  • Caco-2
  • In vitro
  • Microfluidic and screening
  • Small intestine

Cite this

Jochems, Paulus G.M. ; van Bergenhenegouwen, Jeroen ; van Genderen, Anne Metje ; Eis, Sophie T. ; Wilod Versprille, Livia J.F. ; Wichers, Harry J. ; Jeurink, Prescilla V. ; Garssen, Johan ; Masereeuw, Rosalinde. / Development and validation of bioengineered intestinal tubules for translational research aimed at safety and efficacy testing of drugs and nutrients. In: Toxicology in Vitro. 2019 ; Vol. 60. pp. 1-11.
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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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author = "Jochems, {Paulus G.M.} and {van Bergenhenegouwen}, Jeroen and {van Genderen}, {Anne Metje} and Eis, {Sophie T.} and {Wilod Versprille}, {Livia J.F.} and Wichers, {Harry J.} and Jeurink, {Prescilla V.} and Johan Garssen and Rosalinde Masereeuw",
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Jochems, PGM, van Bergenhenegouwen, J, van Genderen, AM, Eis, ST, Wilod Versprille, LJF, Wichers, HJ, Jeurink, PV, Garssen, J & Masereeuw, R 2019, 'Development and validation of bioengineered intestinal tubules for translational research aimed at safety and efficacy testing of drugs and nutrients', Toxicology in Vitro, vol. 60, pp. 1-11. https://doi.org/10.1016/j.tiv.2019.04.019

Development and validation of bioengineered intestinal tubules for translational research aimed at safety and efficacy testing of drugs and nutrients. / Jochems, Paulus G.M.; van Bergenhenegouwen, Jeroen; van Genderen, Anne Metje; Eis, Sophie T.; Wilod Versprille, Livia J.F.; Wichers, Harry J.; Jeurink, Prescilla V.; Garssen, Johan; Masereeuw, Rosalinde.

In: Toxicology in Vitro, Vol. 60, 10.2019, p. 1-11.

Research output: Contribution to journalArticleAcademicpeer-review

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T1 - Development and validation of bioengineered intestinal tubules for translational research aimed at safety and efficacy testing of drugs and nutrients

AU - Jochems, Paulus G.M.

AU - van Bergenhenegouwen, Jeroen

AU - van Genderen, Anne Metje

AU - Eis, Sophie T.

AU - Wilod Versprille, Livia J.F.

AU - Wichers, Harry J.

AU - Jeurink, Prescilla V.

AU - Garssen, Johan

AU - Masereeuw, Rosalinde

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N2 - 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.

AB - 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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KW - Microfluidic and screening

KW - Small intestine

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DO - 10.1016/j.tiv.2019.04.019

M3 - Article

VL - 60

SP - 1

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JO - Toxicology in Vitro

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SN - 0887-2333

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