Development of a new microfluidic platform integrating co-cultures of intestinal and liver cell lines

• Published in: Toxicology in vitro Vol. 28; no. 5; pp. 885 - 895
• Main Authors: Bricks, Thibault, Paullier, Patrick, Legendre, Audrey, Fleury, Marie-José, Zeller, Perrine, Merlier, Franck, Anton, Pauline M., Leclerc, Eric
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.08.2014; Elsevier
• Subjects: Acetaminophen - metabolism; Bioreactors; Caco-2 Cells; Caco-2 TC7; Co-cultures; Coculture Techniques; Cytochrome P-450 CYP1A1 - metabolism; Drug screening; Hep G2 Cells; HepG2 C3A; Humans; Intestinal Absorption; Life Sciences; Liver - metabolism; Microfluidic biochips; Microfluidics - methods; Phenacetin; Phenacetin - metabolism; Co-cultures; Phenacetin; Microfluidic biochips; Drug screening; Caco-2 TC7; HepG2 C3A
• ISSN: 0887-2333; 1879-3177
• DOI: 10.1016/j.tiv.2014.02.005

[Display omitted] •Integration of cell culture transwells and microfluidic biochip in a platform called IIDMP.•Dynamic intestine liver coculture model.•First pass metabolism of phenacetin investigation.•Higher metabolic performance of the bioreactor when compared the Petri coculture.•Step toward organ to organ interaction and ADME processes modeling in vitro. We developed a new biological model to mimic the organ–organ interactions between the intestine and the liver. We coupled polycarbonate cell culture inserts and microfluidic biochips in an integrated fluidic platform allowing dynamic co-cultures (called IIDMP for Integrated Insert in a Dynamic Microfluidic Platform). The intestinal compartment was simulated using Caco-2 TC7 cells and the liver one by HepG2 C3A. We showed that Caco-2 TC7 viability, barrier integrity and functionality (assessed by paracellular and active transport), were not altered during co-cultures in the bioreactor in comparison with the conventional insert Petri cultures. In parallel, the viability and metabolism of the HepG2 C3A cells were maintained in the microfluidic biochips. Then, as proof of concept, we used the bioreactor to follow the transport of phenacetin through the intestinal barrier and its metabolism into paracetamol by the CYP1A of the HepG2 C3A cells. Our results demonstrated the performance of this bioreactor with cell co-cultures compared to static co-culture controls in which weak biotransformation into paracetamol was detected. Our study illustrated the interest of such a bioreactor combining the advantages of a cell culture barrier and of liver microfluidic cultures in a common framework for in vitro studies.