State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology

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Natalie Alépée
Anthony Bahinski
Mardas Daneshian
Bart De Wever
Ellen Fritsche
Alan Goldberg
Jan Hansmann
Thomas Hartung
John Haycock
Helena T. Hogberg
Lisa Hoelting
Jens M. Kelm
Suzanne Kadereit
Emily McVey
Robert Landsiedel
Marcel Leist
Marc Lübberstedt
Fozia Noor
Christian Pellevoisin
Dirk Petersohn
Uwe Pfannenbecker
Kerstin Reisinger
Tzutzuy Ramirez
Barbara Rothen-Rutishauser
Monika Schäfer-Korting
Katrin Zeilinger
Marie-Gabriele Zurich


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.

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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 (Nov. 2014), 441-477. DOI:

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