A microfluidic chip based model for the study of full thickness human intestinal tissue using dual flow

Dawson, Amy; Dyer, Charlotte E.; MacFie, John; Davies, J.; Karsai, Laszlo; Greenman, John; Jacobsen, Morten

doi:10.1063/1.4964813

Cited by 53 publications

(47 citation statements)

References 38 publications

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“…A different type of bioreactor was used to house full thickness intestinal biopsies and perfuse media over the luminal and serosal sides, maintaining viability for up to 72 h. 124 Although this type of ex vivo device may aid in studying certain diseases, the complexity of full thickness intestinal tissue complicates the analysis of experimental results and makes certain mechanisms difficult to identify.…”

Section: Bioreactorsmentioning

confidence: 99%

In VitroModels of the Small Intestine: Engineering Challenges and Engineering Solutions

Hewes

Wilson

Estes

et al. 2020

Tissue Engineering Part B: Reviews

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Pathologies affecting the small intestine contribute significantly to the disease burden of both the developing and the developed world, which has motivated investigation into the disease mechanisms through in vitro models. Although existing in vitro models recapitulate selected features of the intestine, various important aspects have often been isolated or omitted due to the anatomical and physiological complexity. The small intestine's intricate microanatomy, heterogeneous cell populations, steep oxygen gradients, microbiota, and intestinal wall contractions are often not included in in vitro experimental models of the small intestine, despite their importance in both intestinal biology and pathology. Known and unknown interdependencies between various physiological aspects necessitate more complex in vitro models. Microfluidic technology has made it possible to mimic the dynamic mechanical environment, signaling gradients, and other important aspects of small intestinal biology. This review presents an overview of the complexity of small intestinal anatomy and bioengineered models that recapitulate some of these physiological aspects. Keywords: gut-on-a-chip, microfluidic models of intestine, small intestine model, tissue engineered intestine Impact Statement There is a need for improved cell culture models of the small intestine. To develop such models, it is necessary to give engineers a better understanding of intestinal biology, and conversely, to give biologists an idea of what is possible with microfluidic devices and biomaterial platforms. This work provides a detailed overview of aspects of intestinal biology that are important for tissue engineers to understand when designing models of the small intestine and provides a summary of current approaches. This review highlights both unique and common features of various strategies for modeling the intestinal cell environment, not only using microfluidic chip-based systems but also several elegant designs that use a materials-based static culture approach.

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Section: Bioreactorsmentioning

confidence: 99%

In VitroModels of the Small Intestine: Engineering Challenges and Engineering Solutions

Hewes

Wilson

Estes

et al. 2020

Tissue Engineering Part B: Reviews

View full text Add to dashboard Cite

show abstract

“…123 Disease models have been presented based on static or perfused transwell cultures as well as organoids, whereas the short life-span of tissue slices prohibits the induction of intestinal pathologies ex vivo and is thus limited to tissue samples obtained from already injured intestines. 124 Key advantages of organoid cultures for the study of intestinal diseases are the possibility to expand cells isolated from patient biopsies almost unlimitedly, thus allowing high-throughput screening studies in a phenotypically relevant human context. Intestinal organoids are susceptible to infection with rotavirus, echovirus 11, coxsackie virus B1 and enterovirus 71, whereas they replicate only poorly and do not induce antiviral and inflammatory signaling in intestinal cell lines.…”

Section: Disease-modelingmentioning

confidence: 99%

The Past, Present and Future of Intestinal In Vitro Cell Systems for Drug Absorption Studies

Youhanna

Lauschke

2021

Journal of Pharmaceutical Sciences

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The intestinal epithelium acts as a selective barrier for the absorption of water, nutrients and orally administered drugs. To evaluate the gastrointestinal permeability of a candidate molecule, scientists and drug developers have a multitude of cell culture models at their disposal. Static transwell cultures constitute the most extensively characterized intestinal in vitro system and can accurately categorize molecules into low, intermediate and high permeability compounds. However, they lack key aspects of intestinal physiology, including the cellular complexity of the intestinal epithelium, flow, mechanical strain, or interactions with intestinal mucus and microbes. To emulate these features, a variety of different culture paradigms, including microfluidic chips, organoids and intestinal slice cultures have been developed. Here, we provide an updated overview of intestinal in vitro cell culture systems and critically review their suitability for drug absorption studies. The available data show that these advanced culture models offer impressive possibilities for emulating intestinal complexity. However, there is a paucity of systematic absorption studies and benchmarking data and it remains unclear whether the increase in model complexity and costs translates into improved drug permeability predictions. In the absence of such data, conventional static transwell cultures remain the current gold-standard paradigm for drug absorption studies.

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“…Several labs have attempted to build “gut-on-a-chip” systems starting from cell lines or stem cells (see review of gut and microbiota on a chip 119 ), but these systems often lack critical biomolecular interactions with ECM, bacteria, and immune cells. A team led by Greenman and Jacobsen designed a “dual flow” PDMS device to independently perfuse the luminal (innermost) and serosal (external) sides of full-thickness human intestinal tissue for up to 72 h 120 . Physiologically relevant maintenance of viability, cell proliferation, and calproctin levels (a measure of the inflammatory state) was demonstrated throughout the experiment.…”

Section: In Vitro Studiesmentioning

confidence: 99%

Microfluidics for interrogating live intact tissues

et al. 2020

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The intricate microarchitecture of tissues – the “tissue microenvironment” – is a strong determinant of tissue function. Microfluidics offers an invaluable tool to precisely stimulate, manipulate, and analyze the tissue microenvironment in live tissues and engineer mass transport around and into small tissue volumes. Such control is critical in clinical studies, especially where tissue samples are scarce, in analytical sensors, where testing smaller amounts of analytes results in faster, more portable sensors, and in biological experiments, where accurate control of the cellular microenvironment is needed. Microfluidics also provides inexpensive multiplexing strategies to address the pressing need to test large quantities of drugs and reagents on a single biopsy specimen, increasing testing accuracy, relevance, and speed while reducing overall diagnostic cost. Here, we review the use of microfluidics to study the physiology and pathophysiology of intact live tissues at sub-millimeter scales. We categorize uses as either in vitro studies – where a piece of an organism must be excised and introduced into the microfluidic device – or in vivo studies – where whole organisms are small enough to be introduced into microchannels or where a microfluidic device is interfaced with a live tissue surface (e.g. the skin or inside an internal organ or tumor) that forms part of an animal larger than the device. These microfluidic systems promise to deliver functional measurements obtained directly on intact tissue – such as the response of tissue to drugs or the analysis of tissue secretions – that cannot be obtained otherwise.

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A microfluidic chip based model for the study of full thickness human intestinal tissue using dual flow

Cited by 53 publications

References 38 publications

In VitroModels of the Small Intestine: Engineering Challenges and Engineering Solutions

In VitroModels of the Small Intestine: Engineering Challenges and Engineering Solutions

The Past, Present and Future of Intestinal In Vitro Cell Systems for Drug Absorption Studies

Microfluidics for interrogating live intact tissues

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