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

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

Research output: Contribution to journalReview articlepeer-review

185 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)441-77
Number of pages37
JournalAltex
Volume31
Issue number4
DOIs
Publication statusPublished - 2014

Keywords

  • Animal Testing Alternatives/methods
  • Animals
  • Biological Assay/instrumentation
  • Cell Culture Techniques/instrumentation
  • Lab-On-A-Chip Devices
  • Models, Biological

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