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Applied Pharmaceutical Toxicology (APT)

May 10, 2021 — May 11, 2021
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Synopsis

We are proud to be a sponsor at this year’s Applied Pharmaceutical Toxicology virtual event. APT is hosted by The Boston Society, an internationally recognized NON-PROFIT organization dedicated to bringing the best scientific ideas to industrial practice through focused, timely workshops and conferences.

Speaker Spotlight

Sushma Jadalannagari

Senior Scientist, Emulate

Abstract

Traditional in vitro systems fail to replicate the three-dimensional cytoarchitecture and functional complexity of the small intestine, which is an important site for drug and nutrient absorption, digestion, secretion and elimination along with hosting the intestinal microbiome. The poor accuracy of in vitro models represents a significant challenge in the drug development pipeline. To overcome this, we developed a human Duodenum Intestine-Chip that combines healthy intestinal organoids on a microfluidic chip with tissue-specific human intestinal microvascular endothelial cells cultured in a parallel microchannel under flow and cyclic deformation. The physiological microenvironment established on the Duodenum Intestine-Chip supports the formation of villi-like projections lined by polarized epithelial cells with mature tight junctional networks and that undergo multi-lineage differentiation into the major epithelial cell subtypes such as absorptive enterocytes, enteroendocrine, Paneth, and goblet cells. Transcriptomic analysis reveals the Intestine-Chip more closely aligns with human duodenum tissue in vivo than 3D organoids. This correlates with physiological expression of functional intestinal drug transporters such as MDR1, BCRP and PEPT1 including drug mediated induction of CYP3A4. Further, the Duodenum Intestine-Chip demonstrates drug induced toxicity and barrier disruption, after treatment with the tool compounds indomethacin and 5-fluorouracil. In addition, we also show that this Duodenum Intestine-Chip can support long-term probiotic bacterial co-culture with lactobacillus rhamnosus GG. Thus, our human Duodenum Intestine-Chip can be used as a model for preclinical drug assessment in a more human relevant model. 

About Emulate

Emulate Inc. is a privately held company that creates advanced in vitro models for understanding how diseases, medicines, chemicals, and foods affect human health. Our lab-ready Human Emulation System® includes three components: Zoë® Culture Module, Organ-Chips, and analytical software applications. The platform provides a window into the inner workings of human biology and disease—offering researchers a new technology designed to predict human response with greater precision and detail than conventional cell culture or animal-based experimental testing. Each of the Emulate proprietary Organ-Chip models—including the liver, intestine, and kidney—contains tiny hollow channels lined with tens of thousands of living human cells and tissues and is approximately the size of an AA battery. An Organ-Chip is a living, microengineered environment that recreates the natural physiology and mechanical forces that cells experience within the human body. Our founding team pioneered the Organs-on-Chips technology at the Wyss Institute for Biologically Inspired Engineering at Harvard University. Emulate holds the worldwide exclusive license from Harvard University to a robust and broad intellectual property portfolio for the Organs-on-Chips technology and related systems. For more information, please visit emulatebio.com.

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