Engineered Liver and Intestine Platforms for Modeling Physiology and Disease

The intestine and liver are connected in vivo via a recirculating blood supply called the gut-liver axis, which plays a critical role in nutrient/drug absorption and metabolism. Given the diversity of roles the liver plays, there is a need for robust in vitro models capable of recapitulating changes in liver function due to cues from other organs, such as the intestine, or global physical conditions such as chronic disease or pregnancy. Although animal models have provided insight into the mechanisms behind gut-liver crosstalk, species-specific differences in gut microbiome and liver metabolic profile limit their applicability to humans. Furthermore, most in vitro models utilize immortalized tumor cell lines or de-differentiated primary cell monolayers, failing to recapitulate in vivo functionality fully. Here, we explore the development and functional characterization of coupled intestine and liver models using primary human cells. We then utilize this intestine-liver model to elucidate diseased phenotypes of cells under inflammatory stimulation, hypothesizing that underlying organ-organ crosstalk like that observed in vivo would be reproduced. Pregnancy was also identified as a whole-body condition that causes dramatic changes in liver function - particularly hepatocyte cytochrome (CYP) P450 enzyme activity, which can alter drug pharmacokinetics. Although in vivo mouse models of pregnancy are widely utilized, they may be unsuitable to interrogating molecular mediators of pregnancy. We adopt similar engineering techniques to develop mouse liver models from pregnant females (with non-pregnant as a control) to elucidate how paracrine signaling contributes to dramatic changes in liver functions during pregnancy; translation of these findings to human hepatocytes is also explored. In conclusion, engineered models of the intestine and liver are useful for modeling changes in function due to organ-organ crosstalk or global physical conditions such as chronic disease or pregnancy.

Author dc:creator

• Dinithi Nameetha Samarasekera (24400592)

• Engineering
• Biomedical

Statement dc:rights

• In Copyright
• Open Access after 2031-05-01

DOI dc:identifier

https://doi.org/10.25417/uic.32995661.v1

OAI identifier oai:identifier

oai:figshare.com:article/32995661