A Gut-on-Chip and a Liver-on-Chip, or the combination of both model systems on an integrated platform requires a careful considerations of the minimal organ functionality that needs to be emulated in vitro. For several reasons innovative experimental models are needed, for instance to:
- understand the course of intestinal and liver diseases
Better understand the natural course of both intestinal and liver diseases. For instance celiac disease, Crohn disease and other inflammatory bowel diseases. Inflammatory liver diseases that include fibrotic processes are still not fully understood, and clearly lack robust human like in vitro models, hindering our current understanding of the onset and mechanisms of disease.
- predict human responses to xenobiotics
Innovative toxicological research aims to reveal mechanism of adverse reactions, also termed adverse outcome pathways. To adequately predict human responses to xenobiotics it is key to find the balance between highly standardized experimental models (with limited between laboratory variability) and human organ functioning.
- develope a viable intestinal microbiome-on-chip
The intestinal microbiome is key to maintain healthy life. We are yet only beginning to discover the intrinsic interactions, not only between the intestinal microbiome and intestinal tissues, but importantly also with other organ systems in our body (liver, immunesystem and brain). Including a viable intestinal microbiome-on-chip is both a technological and bio engineering challenge.
- test individual response on food ingredients and drug
Individual responses to food ingredients and specific drugs vary greatly. Therefore personalized models, that includes personalized microbiomes and stem cell-based in vitro models are needed. Taking into account individual epigenetic and genetic background is a key challenge for this.
hDMT partners are working on these and other challenges related to Gut-Liver-on chip models. It includes partners with key expertise on genomics, stem cell biology, toxicology and micro(fluidic)technology.
Coupling cultured bacteria and organs-on-chip offers a high potential to conduct individual-based drug testing, by taking into consideration both an individual’s own genome and his or her metagenome. (source: Protein Cell 2018)
The steps from patient or healthy individual to human induced pluripotent stem cell (hiPSC)-derived intestinal organoids and intestinal barrier-on-chip. (source: UEGJournal (2019)