Organotypic Cultures of Hepg2 Cells for In Vitro Toxicity Studies
Daniel Mueller, Anika Koetemann and Fozia Noor*
Biochemical Engineering, Geb. A1 5, Saarland University, D-66123 Saarbruecken, Germany
- *Corresponding Author:
- Fozia Noor
Biochemical Engineering Institute
Saarland University, Campus A 1 5
D-66123 Saarbruecken, Germany
E-mail: [email protected]
Received Date: November 01, 2011; Accepted Date: December 08, 2011; Published Date: December 09, 2011
Citation: Mueller D, Koetemann A, Noor F (2011) Organotypic Cultures of Hepg2 Cells for In Vitro Toxicity Studies. J Bioeng Biomed Sci S2:002. doi:10.4172/2155-9538.S2-002
Copyright: © 2011 Mueller D. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Tissue engineering of human liver cells in a three dimensional cell culture system could improve pharmacological studies in terms of drug metabolism, drug toxicity or adverse drug effects by mimicking the in vivo situation. In this study, we produced 3D organotypic cultures of HepG2 cells using the hanging drop method. 250 – 8000 seeded cells formed organotypic cultures within 2–3 days which increased in size during the first week. Viability and metabolic parameters (glucose, lactate) were analyzed during almost three weeks of cultivation. Liver specific albumin production was higher in the organotypic cultures as compared to both monolayer and collagen-sandwich cultures. Amino acid quantification revealed high production of glutamate as well as uptake of glutamine, alanine and branched-chain amino acids. CYP1A induction capacity was significantly improved by organotypic cultivation. The acute toxicity (24 h) of tamoxifen, an anti-cancer drug, was lower in the 3D cultures as compared to monolayer and collagen-sandwich cultures. This could be explained by a higher drug efflux through membrane transporter (MRP-2). We conclude that the engineered HepG2 cultures could be used for the investigation of CYP450 induction, anti-cancer drug effects and for the study of chemotherapy resistance. Applied to other cell types such as the human primary cells these 3D organotypic cultures may have potential in long term toxicity screening of compounds.