A microfluidic organotypic device for culture of mammalian intestines<i>ex vivo</i>

Richardson, Alec; Schwerdtfeger, Luke; Eaton, Diana; McLean, Ian C.; Henry, Charles S.; Tobet, Stuart A.

doi:10.1039/c9ay02038a

Cited by 31 publications

(45 citation statements)

References 45 publications

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“…Finally, microdissected tissue, although exhibiting little or no oxygen depletion, could always be used inside hypoxic chambers to test the treatment response as a function of oxygen availability. They form, as such, an interesting alternative to tissue slices [9,64]. However, the varying and fluctuating levels of oxygenation seen in vivo and the subsequent cell responses to such fluctuations cannot be modeled using these in vitro assays.…”

Section: Discussionmentioning

confidence: 99%

Microdissected Tissue vs Tissue Slices—A Comparative Study of Tumor Explant Models Cultured On-Chip and Off-Chip

Dorrigiv

Simeone

Communal

et al. 2021

Cancers

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Predicting patient responses to anticancer drugs is a major challenge both at the drug development stage and during cancer treatment. Tumor explant culture platforms (TECPs) preserve the native tissue architecture and are well-suited for drug response assays. However, tissue longevity in these models is relatively low. Several methodologies have been developed to address this issue, although no study has compared their efficacy in a controlled fashion. We investigated the effect of two variables in TECPs, specifically, the tissue size and culture vessel on tissue survival using micro-dissected tumor tissue (MDT) and tissue slices which were cultured in microfluidic chips and plastic well plates. Tumor models were produced from ovarian and prostate cancer cell line xenografts and were matched in terms of the specimen, total volume of tissue, and respective volume of medium in each culture system. We examined morphology, viability, and hypoxia in the various tumor models. Our observations suggest that the viability and proliferative capacity of MDTs were not affected during the time course of the experiments. In contrast, tissue slices had reduced proliferation and showed increased cell death and hypoxia under both culture conditions. Tissue slices cultured in microfluidic devices had a lower degree of hypoxia compared to those in 96-well plates. Globally, our results show that tissue slices have lower survival rates compared to MDTs due to inherent diffusion limitations, and that microfluidic devices may decrease hypoxia in tumor models.

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Section: Discussionmentioning

confidence: 99%

Microdissected Tissue vs Tissue Slices—A Comparative Study of Tumor Explant Models Cultured On-Chip and Off-Chip

Dorrigiv

Simeone

Communal

et al. 2021

Cancers

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“… 12 The establishment of a controlled oxygen gradient in intestine-on-chip systems recently was shown to support direct co-culture of intestinal epithelial cells with complex communities of anaerobic and aerobic human commensal gut bacteria 11 and their sustained viability in long-term culture. 34 , 29 …”

Section: Oxygen Gradientmentioning

confidence: 99%

Organ-on-Chip Approaches for Intestinal 3D In Vitro Modeling

Pimenta

Ribeiro²,

Almeida

et al. 2022

Cellular and Molecular Gastroenterology and Hepatology

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The intestinal epithelium has one of the highest turnover rates in the human body, which is supported by intestinal stem cells. Culture models of intestinal physiology have been evolving to incorporate different tissue and microenvironmental elements. However, these models also display gaps that limit their similarity with native conditions. Microfluidics technology arose from the application of microfabrication techniques to fluid manipulation. Recently, microfluidic approaches have been coupled with cell culture, creating self-contained and modular in vitro models with easily controllable features named organs-on-chip. Intestine-on-chip models have enabled the recreation of the proliferative and differentiated compartments of the intestinal epithelium, the long-term maintenance of commensals, and the intraluminal perfusion of organoids. In addition, studies based on human primary intestinal cells have shown that these systems have a closer transcriptomic profile and functionality to the intestine in vivo, when compared with other in vitro models. The design flexibility inherent to microfluidic technology allows the simultaneous combination of components such as shear stress, peristalsis-like strain, 3-dimensional structure, oxygen gradient, and co-cultures with other important cell types involved in gut physiology. The versatility and complexity of the intestine-on-chip grants it the potential for applications in disease modeling, host-microbiota studies, stem cell biology, and, ultimately, the translation to the pharmaceutical industry and the clinic as a reliable high-throughput platform for drug testing and personalized medicine, respectively. This review focuses on the physiological importance of several components that have been incorporated into intestine-on-chip models and highlights interesting features developed in other types of in vitro models that might contribute to the refinement of these systems.

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“…However, the configurations were different in size and structure from the surface of the SI tract, which were assumed to be important for the fluid flow field in the SI tracts. On the other hand, microfluidic devices utilizing the natural features of full thickness intestinal tissues ex vivo were proposed [23][24][25][26]. Those devices have a sheet of a dissected intestinal tissue in the channel.…”

Section: Introductionmentioning

confidence: 99%

“…They enable tissue culture for 3 days to monitor some functions in living intestinal tissues. In addition, microfluidic devices enable the observation of the intestinal tissue ex vivo [26]. However, the observations are only at the macro scale, and the analyses are performed only by the measurement of effluent from the outlet of the device.…”

Section: Introductionmentioning

confidence: 99%

Microfluidic Device Using Mouse Small Intestinal Tissue for the Observation of Fluidic Behavior in the Lumen

2021

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The small intestine has the majority of a host’s immune cells, and it controls immune responses. Immune responses are induced by a gut bacteria sampling process in the small intestine. The mechanism of immune responses in the small intestine is studied by genomic or histological techniques after in vivo experiments. While the distribution of gut bacteria, which can be decided by the fluid flow field in the small intestinal tract, is important for immune responses, the fluid flow field has not been studied due to limits in experimental methods. Here, we propose a microfluidic device with chemically fixed small intestinal tissue as a channel. A fluid flow field in the small intestinal tract with villi was observed and analyzed by particle image velocimetry. After the experiment, the distribution of microparticles on the small intestinal tissue was histologically analyzed. The result suggests that the fluid flow field supports the settlement of microparticles on the villi.

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A microfluidic organotypic device for culture of mammalian intestinesex vivo

Abstract: A microfluidic organotypic device that maintains mouse colon explants for up to 72 h in a physiologically relevant environment is reported. The device is easy to assemble and maintains physiologically accurate oxygen concentrations across the tissue.

Cited by 31 publications

References 45 publications

Microdissected Tissue vs Tissue Slices—A Comparative Study of Tumor Explant Models Cultured On-Chip and Off-Chip

Microdissected Tissue vs Tissue Slices—A Comparative Study of Tumor Explant Models Cultured On-Chip and Off-Chip

Organ-on-Chip Approaches for Intestinal 3D In Vitro Modeling

Microfluidic Device Using Mouse Small Intestinal Tissue for the Observation of Fluidic Behavior in the Lumen

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