Human Gut-on-a-Chip Microdevice May Help Overcome Limitations of Animal Models

In this week’s Science First, we’d like to share with you the results of a new study coming from the lab of one of our International Foundation for Ethical Research (IFER) fellowship recipients. The paper describes an important application of the human gut-on-a-chip microdevice — its use as a model for inflammatory bowel diseases, disorders which affect as many as a million Americans.

In Proceedings of the National Academy of Sciences(PNAS), Dr. Hyun Jung Kim of the University of Texas-Austin– mentor of our IFER fellowship recipient Jaewon Lee–and his former colleagues at the Wyss Institute at Harvard University shared exciting findings about how the microfluidic gut-on-a-chip device could be used to model human intestinal diseases in ways that offered improvements over existing cell and animal models. Existing models may actually “seriously hamper the accurate understanding of the initiation and progression of IBD [inflammatory bowel disease],” according to Dr. Kim.

While it is thought that inflammatory bowel diseases are caused by interactions of a number of contributing factors, including gut microbes, immune cells, intestinal cells and issues with the wave-like muscle contractions that help move food in the digestive tract, limitations with existing models have prevented researchers from fully appreciating the contribution of each of these factors to intestinal inflammatory diseases.

However, the gut-on-a-chip microdevice enables the effect of each of these parameters to be studied individually in vitro, to better understand how they contribute to inflammation and overgrowth of bacteria, similar to what is observed in patients with intestinal disorders. Results from the PNAS study identified previously unknown contributions of inflammatory proteins and mechanical motion to intestinal inflammation and demonstrated the ability of the device to enable culture of intestinal cells with living microbes normally found in the gut for up to two weeks, which gave researchers insight into how microbes contribute to human health and disease.

When speaking with Dr. Kim about his work, he shared, “We believe that the human cell-based in vitro microphysiological systems could potentially provide huge opportunities to replace existing animal models or significantly improve the current in vitro 2D cell culture models…because they offer physiological cell/tissue microenvironment (e.g. 3D intestinal villi formation), mechanically dynamic motions and flow (e.g. peristalsis), stable host-microbe ecosystem (e.g. gut microbiome), and organ-level functions (e.g. lumen-capillary tissue-tissue interface) as all are necessary and sufficient to recapitulate the in vivo situation.”

Under Dr. Kim’s guidance, IFER fellowship recipient Jaewon Lee plans to follow up on this “proof-of-principle” study to further understand the effect of different toxic chemical agents in inducing inflammation in the in vitro model, as well as to examine the effect of different potential therapeutics, such as probiotic effects, in the model. Lee may even explore the impact of using different patient samples (cells, microbes, immune components) with the device in an effort to create more personalized models, to create a so called “you-on-a-chip” in the future.

We are proud to support these efforts through IFER and look forward to sharing with you more exciting progress made on this project in the future.

What are your thoughts on the gut-on-a-chip microdevice and its ability to serve as a model for human intestinal inflammatory diseases? Send your question and comments to sciencecorner@navs.org. I look forward to hearing from you.

-Dr. Pam Osenkowski, Director of Science Programs


Related

Human-gut-on-a-chip model offers hope for IBD sufferers
December 15, 2015

[U]ntil now, scientists have been hard pressed to develop new therapies for treating IBDs because they could not replicate the human gut microenvironment in the laboratory. On Monday, the Wyss Institute for Biologically Inspired Engineering at Harvard University announced that its team had created a model of human intestinal inflammation and bacterial overgrowth in a human-gut-on-a-chip.

For more information see: Harvard Gazette


This entry was posted in News and tagged on December 28, 2015.
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