Journal Mobile Options
Table of Contents
Vol. 181, No. 2, 2005
Issue release date: March 2006
Section title: Original Paper
Cells Tissues Organs 2005;181:67–79

The Effect of Three-Dimensional Co-Culture of Hepatocytes and Hepatic Stellate Cells on Key Hepatocyte Functions in vitro

Thomas R.J. · Bhandari R. · Barrett D.A. · Bennett A.J. · Fry J.R. · Powe D. · Thomson B.J. · Shakesheff K.M.
University of Nottingham, Nottingham, UK
email Corresponding Author

Prof. Kevin M. Shakesheff

School of Pharmacy, University of Nottingham

Nottingham, NG7 2RD (UK)

Tel. +44 115 951 5104, Fax +44 115 951 5122


Do you have an account?

Register and profit from personalized services (MyKarger) Login Information

Please create your User ID & Password

Contact Information

I have read the Karger Terms and Conditions and agree.


In this study, we demonstrate the ability of a three-dimensional co-culture model to preserve some key aspects of differentiated hepatocyte function in vitro. Freshly isolated rat hepatocytes in co-culture with activated stellate cells rapidly aggregate to form well-defined viable spheroids. After 5 days in culture, the spheroids have a complex extracellular matrix support and hepatic ultrastructure including bile canaliculi, tight junctions, desmosomes and lipid storage. Co-culture spheroids have superior cytochrome P450 (CYP450) 3A and 2B function, and increased inducibility of 2B function, relative to a range of hepatocyte monoculture techniques (high-performance liquid chromatography of testosterone metabolites). Increased function in co-culture is supported by greater expression of CYP450 3A23, 1A2, and 2E1 mRNA relative to monoculture (reverse transcriptase quantitative polymerase chain reaction). Also, high hepatocyte growth factor mRNA expression in co-culture suggests a post-traumatic, or possibly regenerative, environment. A preliminary study of human hepatocytes co-cultured with rat stellate cells demonstrated prolonged function of CYP450 3A4, 2C19 and 2C9. This study shows that stellate cells facilitate spheroid formation, influence spheroid architecture, and are an effective method of preserving some aspects of hepatocyte function in the early stage of culture.

© 2005 S. Karger AG, Basel

Article / Publication Details

First-Page Preview
Abstract of Original Paper

Accepted: 12/5/2005
Published online: 7/4/2008

Number of Print Pages: 13
Number of Figures: 8
Number of Tables: 2

ISSN: 1422-6405 (Print)
eISSN: 1422-6421 (Online)

For additional information:

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher or, in the case of photocopying, direct payment of a specified fee to the Copyright Clearance Center.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.