State-of-the-Art of 3D Cultures (Organs-on-a-Chip) in Safety Testing and Pathophysiology

Authors

Natalie Alépée, L’Oréal R&I
Anthony Bahinski, Harvard University
Mardas Daneshian, University of Konstanz
Bart De Wever, The Alexandra Association
Alan Goldberg, Johns Hopkins University
Jan Hansmann, University Hospital Wuerzburg
Thomas Hartung, University of Konstanz
John Haycock, University of Sheffield
Helena T. Hogberg, Johns Hopkins University
Lisa Hoelting, University of Konstanz
Jens M. Kelm, InSphero AG
Suzanne Kadereit, University of Konstanz
Emily McVey, Board for the Authorization of Plant Protection Products and Biocides (The Netherlands)
Robert Landsiedel, BASF SE
Marcel Leist, University of Konstanz
Marc Lübberstedt, Berlin-Brandenburg Center for Regenerative Therapies (BCRT)
Fozia Noor, Saarland University
Christian Pellevoisin, L’Oréal R&I
Dirk Petersohn, Henkel AG & Co KGaA
Uwe Pfannenbecker, Beiersdorf AG
Kerstin Reisinger, Henkel AG & Co KGaA
Tzutzuy Ramirez, BASF SE
Barbara Rothen-Rutishauser, University of Fribourg
Monika Schäfer-Korting, Freie Universität Berlin
Katrin Zeilinger, Berlin-Brandenburg Center for Regenerative Therapies (BCRT)
Marie-Gabriele Zurich, University of Lausanne

Document Type

Report

Publication Date

4-2014

Abstract

Integrated approaches using different in vitro methods in combination with bioinformatics can (i) increase the success rate and speed of drug development; (ii) improve the accuracy of toxicological risk assessment; and (iii) increase our understanding of disease. Three-dimensional (3D) cell culture models are important building blocks of this strategy which has emerged during the last years. The majority of these models are organotypic, i.e., they aim to reproduce major functions of an organ or organ system. This implies in many cases that more than one cell type forms the 3D structure, and often matrix elements play an important role. This review summarizes the state of the art concerning commonalities of the different models. For instance, the theory of mass transport/metabolite exchange in 3D systems and the special analytical requirements for test endpoints in organotypic cultures are discussed in detail. In the next part, 3D model systems for selected organs – liver, lung, skin, brain – are presented and characterized in dedicated chapters. Also, 3D approaches to the modeling of tumors are presented and discussed. All chapters give a historical background, illustrate the large variety of approaches, and highlight up- and downsides as well as specific requirements. Moreover, they refer to the application in disease modeling, drug discovery and safety assessment. Finally, consensus recommendations indicate a roadmap for the successful implementation of 3D models in routine screening. It is expected that the use of such models will accelerate progress by reducing error rates and wrong predictions from compound testing.

Comments

open access report

Recommended Citation

Alépée, N., Bahinski, A., Daneshian, M., De Wever, B., Fritsche, E., Goldberg, A., Hansmann, J., Hartung, T., Haycock, J., Hogberg, H., Hoelting, L., Kelm, J., Kadereit, S., McVey, E., Landsiedel, R., Leist, M., Lübberstedt, M., Noor, F., Pellevoisin, C., Petersohn, D., Pfannenbecker, U., Reisinger, K., Ramirez, T., Rothen-Rutishauser, B., Schäfer-Korting, M., Zeilinger, K. and Zurich, M.-G. (2014) “State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology”, ALTEX - Alternatives to animal experimentation, 31(4), pp. 441-477. doi: 10.14573/altex.1406111.