Development of an in vitro microscale cell culture analog of the gastrointestinal tract

BIOT 212

Gretchen J. McAuliffe, gjm23@cornell.edu1, Jung Y. Chang, jyc34@cornell.edu1, Raymond P. Glahn, rpg3@cornell.edu2, and Michael L. Shuler, mls50@cornell.edu1. (1) School of Chemical and Biomolecular Engineering, Cornell University, 120 Olin Hall, Ithaca, NY 14853, (2) Department of Food Science, Cornell University, US Plant, Soil and Nutrition Laboratory, Ithaca, NY 14853
Our group has developed microscale cell culture analogs (μCCAs) used to study the metabolism and toxicity of a chemical or drug. These in vitro devices are physical replicas of physiologically based pharmacokinetic models that combine microfabrication and cell culture (Biotechnol. Prog., 20 (1), 338-345, 2004). The goal of this project is to add an independent GI tract μCCA to a multi-chamber “body” μCCA. The GI tract μCCA consists of two chambers separated by a microporous membrane on which epithelial cells are cultured. Compounds of interest are subjected to an in vitro digestion then pumped through the top chamber, allowing drug to be absorbed through the epithelial layer and circulated into the “body” μCCA. The μCCAs have been used to recreate the toxic effects of acetaminophen. Preliminary results show that when ethanol, a cytochrome P450 2E1 inducer, is added to the culture medium the toxic effects of acetaminophen are amplified.