Article | August 6, 2021

Evaluating Microbiome Therapies With Intestinal Cell Models

By Scott Magness, Ph.D., Chief Science Offi cer and Co-Founder, Altis Biosystems

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Stem cells are implicated in a variety of disease process. Before it is possible to understand what those roles are, it is necessary to understand the basic biology of stem cells: how they work and how they renew themselves and differentiate. With that information in hand, it is possible to investigate the differences between normal physiology and disease states to determine what goes wrong with stem cells during disease processes and ultimately to evaluate how different treatments for disease can impact stem cells.

For instance, radiation or chemotherapy treatments for cancer can have significant off-target effects involving intestinal and colonic stem cells, because the gut is one of the first areas of the body negatively affected by these therapies. With sufficient understanding of the normal physiology of these stem cells, there is considerable potential to preempt toxicities that occur as the result of various therapeutic regimens.

The obvious first step in this endeavor was the development of platforms based on primary human epithelial stem cells that can be used for drug screening. Historically, colonic cancer cells (Caco-2) have been used for decades to study drug absorption in the small intestine, but these models do not always mimic normal physiology, and many failures of Caco-2 as a preclinincal model have resulted. By contrast, new methods using gut epithelial tissue cultured from patient stem cells could be used not only to investigate their physiology but also construct a more effective platform for screening drug candidates.

The microbiome has been shown to play roles in many different disease processes and is implicated in many more, from infectious and gastrointestinal diseases to autoimmune and neurological disorders. Advanced models of the gut leveraging intestinal and colonic stem cells are enabling the development of more reliable and robust systems for evaluating the impact of changes in the microbiome on gut health and screening potential drug candidates, including small molecules, biologics, and live biotherapeutics.

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