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Gut Organ Chip Developed for Realistic Conditions

Human gut microbes

Microbes in the human gut (Wyss Institute, Harvard University)

13 May 2019. A bio-engineering group created a chip device that simulates human intestine tissue in the lab, but under more realistic conditions than before. A team from the Wyss Institute for Biologically Inspired Engineering at Harvard University describes the device in today’s issue of the journal Nature Biomedical Engineering (paid subscription required).

This latest advance in organs-on-chips builds on the Wyss Institute’s work in the field, including earlier gut-on-a-chip devices. Organs-on-chips are small flexible polymer plastic devices with fine channels etched in the surface or drilled through, lined with live tissue and cells, and designed to simulate the workings of human organs. Three-dimensional tissues on the devices make it possible to predict the behavior of human organs better than animal models like mice, or cells grown in lab cultures. The devices are designed to simulate the flow, dynamics, and environment of complex systems in organs.

A drawback of gut-on-a-chip devices up to now is their inability to simulate the anaerobic, or low-oxygen, state found in parts of the human intestine, where certain microbes thrive. Moreover, this anaerobic environment coexists with oxygen-rich parts of the gut, calling for a device that can simultaneously support both states that interact with each other. This complex device is needed, say the authors to realistically study the workings of the microbiome, or microbial communities in the gut, an emerging focus of biomedical research.

“The major paradigm shift in medicine over the past decade has been the recognition of the huge role that the microbiome plays in health and disease,” says Donald Ingber, director of the Wyss Institute and senior author of the paper in an institute statement. “This new anaerobic intestine chip technology now provides a way to study clinically relevant human host-microbiome interactions at the cellular and molecular levels under highly controlled conditions in vitro,” referring to studies with instruments under lab conditions.

For their new intestine chip, the Wyss Institute researchers took their earlier gut-on-a-chip device and devised parallel channels, both with cells from human intestinal linings and supporting blood vessels. They derived these tissue samples from biopsies or stem cells grown into organoids, or small working tissue models. The team then placed the device in a chamber, enclosing one of the parallel channels, where the oxygen can be drawn out to simulate an anaerobic state, while still remaining connected and interacting with the other channels functioning in oxygen.

The team tested the device with microbes taken from mice and human stool samples. The microbes were injected into the intestinal lining tissue in the chip that developed a mucus layer, much like that found in the intestine. That mucus layer provides a protective seal in the new intestine chip similar to the one found in healthy gut tissue. In addition, the device supported the growth of more than 200 different types of gut bacteria, similar to those found in human stools.

The researchers believe the new, more realistic gut-on-a-chip offers opportunities for personalized drug testing with an individual’s unique gut tissue. “We can culture region-specific intestinal tissue and microbiomes from the same individual to find associations that cause sensitivity or tolerance to specific pathogenic, inflammatory, and systemic diseases,” says postdoctoral researcher and co-first author Francesca Gazzaniga. “With the anaerobic intestine chip, we can also test the direct effects of drugs on the human microbiome before giving them to people.”

Ingber is scientific founder of the company Emulate Inc. developing commercial applications for organs-on-chips, including intestine chips, and chairs its scientific advisory board. As reported by Science & Enterprise in December 2018, Emulate Inc. is designing special versions of its intestine chip as part of an experiment on the International Space Station to test effects of weightlessness on immune functions and bacterial infections in the gastrointestinal tract.

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