title: Improvement of HepG2/C3a cell functions in a microfluidic biochip.
abstract: Current developments in tissue engineering and microtechnology fields allow the use of microfluidic biochip as microtools for in vitro investigations. In the present study, we describe the behavior of HepG2/C3a cells cultivated in a poly(dimethylsiloxane) (PDMS) microfluidic biochip coupled to a perfusion system. Cell culture in the microfluidic biochip for 96 h including 72 h of perfusion provoked a 24 h delay in cell growth compared to plate cultures. Inside the microfluidic biochip, few apoptosis, and necrosis were detected along the culture and 3D cell organization was observed. Regarding the hepatic metabolism, glucose and glutamine consumptions as well as albumin synthesis were maintained. A transcriptomic analysis performed at 96 h of culture using Affymetrix GeneChip demonstrated that 1,025 genes with a fold change above 1.8 were statistically differentially expressed in the microfluidic biochip cultures compared to plate cultures. Among those genes, phase I enzymes involved in the xenobiotic's metabolism such as the cytochromes P450 (CYP) 1A1/2, 2B6, 3A4, 3A5, and 3A7 were up-regulated. The CYP1A1/2 up-regulation was associated with the appearance of CYP1A1/2's activity evidenced by using EROD biotransformation assay. Several phase II enzymes such as sulfotransferases (SULT1A1 and SULT1A2), UDP-glucuronyltransferase (UGT1A1, UGT2B7) and phase III transporters (such as MDR1, MRP2) were also up-regulated. In conclusion, microfluidic biochip could and provide an important insight to exploring the xenobiotic's metabolism. Altogether, these results suggest that this kind of biochip could be considered as a new pertinent tool for predicting cell toxicity and clearance of xenobiotics in vitro.
authors.affiliation: CNRS UMR 6600, Laboratoire de Biomécanique et Bioingénierie, Université de Technologie de Compiègne, Compiègne 60205, France.
authors.forename: Jean Matthieu
authors.initials: JM
authors.lastname: Prot
authors.forename: Caroline
authors.initials: C
authors.lastname: Aninat
authors.forename: Laurent
authors.initials: L
authors.lastname: Griscom
authors.forename: Florence
authors.initials: F
authors.lastname: Razan
authors.forename: Céline
authors.initials: C
authors.lastname: Brochot
authors.forename: Christiane Guguen
authors.initials: CG
authors.lastname: Guillouzo
authors.forename: Cécile
authors.initials: C
authors.lastname: Legallais
authors.forename: Anne
authors.initials: A
authors.lastname: Corlu
authors.forename: Eric
authors.initials: E
authors.lastname: Leclerc
mesh_terms: D000418:Albumins / Q000378:metabolism; D016923:Cell Death; D002460:Cell Line; D002470:Cell Survival; D004129:Dimethylpolysiloxanes; D020869:Gene Expression Profiling; D005947:Glucose / Q000378:metabolism; D005973:Glutamine / Q000378:metabolism; D022781:Hepatocytes / Q000378:metabolism / Q000502:physiology*; D006801:Humans; D044085:Microfluidics / Q000379:methods*; D009757:Nylons; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D000418:Albumins; D004129:Dimethylpolysiloxanes; D009757:Nylons; C085707:poly(dimethylsiloxane)-polyamide copolymer; D005973:Glutamine; D005947:Glucose