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

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

doi:10.1016/j.tiv.2019.04.019

Cited by 23 publications

(31 citation statements)

References 57 publications

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“…After chamber construction, extra cellular matrix (ECM) coating and cell seeding were done as described before with minor changes (13). Here, coating was directly executed in the 3D-chambers, thus 90° turning was excluded from the protocol.…”

Section: Bioengineered Intestinal Tubule Construction Coating Seedimentioning

confidence: 99%

“…Staining protocol for bioengineered intestinal tubules was described previously (13). In short, cells…”

Section: Immunofluorescent Staining and Zonula Occludens-1 Quantificamentioning

confidence: 99%

“…Here, bioengineered intestinal tubules were used as microphysiological gut that were exposed to in vitro digested proteins followed by evaluation of key physiological parameters (13). Three commonly used proteins sources (acidic WPC, egg, soy) and fourteen potential dietary proteins from a variety of sustainable sources (bovine blood plasma, insect (mealworm), pea, corn, wheat, fungi, yeast, potato) were studied and compared to a benchmark whey protein concentrate (WPC).…”

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confidence: 99%

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A combined microphysiological-computational omics approach in dietary protein evaluation

Jochems

Keusters

America

et al. 2020

Preprint

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AbstractThe ever-growing world population puts pressure on food security. To tackle this, waste stream proteins and novel protein sources need to be evaluated for nutritional value, which requires information on digesta peptide composition in comparison to established protein sources and coupling to biological parameters. Here, we present a novel combined experimental and computational approach comparing seventeen protein sources with cow’s whey protein (WPC) as benchmark. In vitro digestion was followed by proteomics analysis and statistical model clustering based on Bayesian Information Criterion. Next, we incorporated functional protein data after evaluating the effects of eighteen protein digests on intestinal barrier integrity, viability, brush border enzyme activity and immune parameters using a bioengineered intestine. Our data show that a holistic approach allows evaluating a dietary protein’s potential for delivery of bioactive peptides, where protein source (animal, plant or novel source-derived) does not seem to be the driving force for clustering.

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Section: Bioengineered Intestinal Tubule Construction Coating Seedimentioning

confidence: 99%

“…Staining protocol for bioengineered intestinal tubules was described previously (13). In short, cells…”

Section: Immunofluorescent Staining and Zonula Occludens-1 Quantificamentioning

confidence: 99%

mentioning

confidence: 99%

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A combined microphysiological-computational omics approach in dietary protein evaluation

Jochems

Keusters

America

et al. 2020

Preprint

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“…The cells in our flow setup exhibited a higher p-cresol metabolic capacity, tighter monolayer formation, improved brush border activity (alkaline phosphatase) and better differentiation in terms of villi formation (Figure 7) compared to previous studies like Jochems et al (2019). Thus, this novel microphysiological system is already a promising tool for studies of the metabolic functions of the intestine.…”

Section: Discussionmentioning

confidence: 58%

“…Various microphysiological systems have been developed that mimic mechanical, structural, and functional properties of the human small intestine (see e.g., Kim and Ingber, 2013 ; Trietsch et al, 2017 ; Kasendra et al, 2018 ; Jochems et al, 2019 ). These devices have already displayed the capability to reproduce organ-level responses and may be transferred to pharmaceutical industries to be implemented in preclinical research and have potential to replace animal studies for e.g., drug screening.…”

Section: Introductionmentioning

confidence: 99%

A Theoretical and Experimental Study to Optimize Cell Differentiation in a Novel Intestinal Chip

Langerak

Ahmed

et al. 2020

Front. Bioeng. Biotechnol.

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Microphysiological systems have potential as test systems in studying the intestinal barrier, in which shear stress is critical for the differentiation of Caco-2 cells into enterocytes. The most commonly used in vitro gut model for intestinal barrier studies is based on trans-well cultures. Albeit useful, these culture systems lack physiological shear stress which is believed to be critical for the differentiation of Caco-2 cells into enterocytes and to form tight monolayers. Conversely, organ-on-chip models have presented themselves as a promising alternative since it provides cells with the required shear stress. To this end, a novel biocompatible 3D-printed microfluidic device was developed. In this device, Caco-2 cells were seeded under physiologically-relevant unidirectional shear stress and compared to cells cultured under gravity-driven flow. Using numerical studies, the flow rate that corresponds to the required shear stress was calculated. Experimental tests were conducted to verify the effect of this on cell differentiation. The experiments clearly showed an enhancement of cell differentiation potential in a unidirectional physiologically-relevant pump-driven flow system (PDFS) as opposed to the simpler bidirectional gravity-driven flow system (GDFS). Additionally, computational modeling of an adapted design confirmed its ability to supply all cells with a more homogeneous shear stress, potentially further enhancing their differentiation. The shear stress in the adapted design can be well-approximated with analytic methods, thus allowing for efficient predictions for all parameter values in the system. The developed novel microfluidic device led to the formation of a tighter monolayer and enhanced functional properties of the differentiated Caco-2 cells, which presents a promising tool for preclinical in vitro testing of drugs in an animal-free platform.

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From fatty hepatocytes to impaired bile flow: Matching model systems for liver biology and disease

Kunst

Niemeijer

Laan

et al. 2020

Biochemical Pharmacology

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

Cited by 23 publications

References 57 publications

A combined microphysiological-computational omics approach in dietary protein evaluation

A combined microphysiological-computational omics approach in dietary protein evaluation

A Theoretical and Experimental Study to Optimize Cell Differentiation in a Novel Intestinal Chip

From fatty hepatocytes to impaired bile flow: Matching model systems for liver biology and disease

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