Human intestinal inflammatory diseases are common and complex conditions that involve interactions between gut microbes, intestinal cells and components of the immune system. While dozens of animal models are available to study gut inflammation, many researchers have come to recognize the limitations of using animals and have started developing human-relevant models, some of which have been supported by NAVS through the International Foundation for Ethical Research (IFER).
A recent study focused on intestinal models has just come from the lab of Dr. Don Ingber at the Wyss Institute in Boston. Dr Ingber was also the mentor of former IFER fellowship recipient Bryan Hassell.
Researchers in Dr. Ingber’s lab developed a sophisticated colon-on-a-chip model. This model incorporates an essential component of the intestine that has previously been challenging to model in vitro: mucus. This gooey substance, which lines the intestinal surface, provides a barrier that protects intestinal cells from bacteria, helping to inhibit inflammation and infection. Researchers know that mucus differs between humans and other species, and that it also differs between different people, making the generation of personalized human gut models even more important.
To do this, researchers in the Ingber lab created a colon-on-a-chip microfluidic device that was lined with patient-derived colon cells. When they flowed a nutrient medium through the channels of the device, the colon cells naturally grew into a continuous sheet and some cells spontaneously differentiated into the cell type which generated mucus.
The researchers predict this functional mini-gut model will help answer questions regarding the role of normal and disease-associated mucus in intestinal diseases and cancer. And because the device can be lined with patient-specific cells, personalized patient models can be developed. This may help identify tailored therapies for people.
“Our in vitro system brings us one step closer to figuring out how individual bacterial species and more complex microbial communities can affect mucus and vice versa, as well as how this complex interplay impacts development of intestinal diseases,” Dr. Ingber noted. “We also now have a testbed to discover new therapeutic drug and probiotic strategies that might prevent or reverse these diseases.”
NAVS sees great promise in the ability of organs-on-chips to provide human-relevant models which will significantly reduce the use of animals in scientific experimentation. We will continue to keep you posted on exciting developments in this area.
Help NAVS continue to support smarter science that advances discovery, innovation and human-relevant solutions without the use of harmful, flawed and costly animal experiments by making a donation today.
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Boettner, B. “Investigating the human intestinal mucus barrier up-close and personal,” Wyss Institute Website. December 3, 2019