December 21, 2015

Human-gut-on-a-chip model offers hope for IBD sufferers

From Harvard Gagette

Human-gut-on-a-chip model offers hope for IBD sufferers

Wyss Institute replicates gut’s microenvironment in the lab, allowing researchers new access

By Kat J. McAlpine, Wyss Institute Communications | December 15, 2015

It’s estimated that as many as a million Americans suffer from inflammatory bowel diseases (IBD) such as ulcerative colitis and Crohn’s disease, which cause mild to severe symptoms that at best can be managed and at worst lead to life-threatening complications.

While abnormal immune responses are largely responsible for these diseases, issues relating to gut microbiome, intestinal epithelial cells, immune components, and the gut’s rhythmic peristalsis motions can also contribute to and exacerbate symptoms. But until 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. The team, co-led by Wyss Institute Founding Director Donald Ingber and core faculty member James Collins, leveraged the institute’s proprietary human-organs-on-chips technology to microengineer the model.

The advance, reported in the Proceedings of the National Academy of Sciences (PNAS), allows scientists to analyze for the first time how normal gut microbes and pathogenic bacteria contribute to immune responses, and to investigate IBD mechanisms in a controlled model that recapitulates human intestinal physiology.

“Chronic inflammation of the intestine is thought to be caused by abnormal interactions between gut microbes, intestinal epithelial cells, and the immune system, but so far it has been impossible to determine how each of these factors contributes to the development of intestinal bowel disease,” said Hyun Jung Kim, former Wyss Technology Development Fellow and first author of the study, speaking about the limitations of conventional in vitro and animal models of bacterial overgrowth and inflammation of the intestines.

The human-gut-on-a-chip technology, however, provides an ideal microenvironment for mimicking the natural conditions of the human intestines in a small-scale, controllable, in vitro platform. The human-gut-on-a-chip was first invented at the Wyss Institute in 2012. Made of a clear, flexible polymer about the size of a computer memory stick, the hollow-channeled microfluidic device simulates the physical structure, microenvironment, peristalsis-like waves and fluid flow of the human intestine.

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