title: State-of-the-art of 3D cultures (organs-on-a-chip) in safety testing and pathophysiology.
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.
authors.affiliation: L'Oréal R&I, Aulnay, France.
authors.forename: Natalie
authors.initials: N
authors.lastname: Alépée
authors.forename: Anthony
authors.initials: A
authors.lastname: Bahinski
authors.forename: Mardas
authors.initials: M
authors.lastname: Daneshian
authors.forename: Bart
authors.initials: B
authors.lastname: De Wever
authors.forename: Ellen
authors.initials: E
authors.lastname: Fritsche
authors.forename: Alan
authors.initials: A
authors.lastname: Goldberg
authors.forename: Jan
authors.initials: J
authors.lastname: Hansmann
authors.forename: Thomas
authors.initials: T
authors.lastname: Hartung
authors.forename: John
authors.initials: J
authors.lastname: Haycock
authors.forename: Helena
authors.initials: H
authors.lastname: Hogberg
authors.forename: Lisa
authors.initials: L
authors.lastname: Hoelting
authors.forename: Jens M
authors.initials: JM
authors.lastname: Kelm
authors.forename: Suzanne
authors.initials: S
authors.lastname: Kadereit
authors.forename: Emily
authors.initials: E
authors.lastname: McVey
authors.forename: Robert
authors.initials: R
authors.lastname: Landsiedel
authors.forename: Marcel
authors.initials: M
authors.lastname: Leist
authors.forename: Marc
authors.initials: M
authors.lastname: Lübberstedt
authors.forename: Fozia
authors.initials: F
authors.lastname: Noor
authors.forename: Christian
authors.initials: C
authors.lastname: Pellevoisin
authors.forename: Dirk
authors.initials: D
authors.lastname: Petersohn
authors.forename: Uwe
authors.initials: U
authors.lastname: Pfannenbecker
authors.forename: Kerstin
authors.initials: K
authors.lastname: Reisinger
authors.forename: Tzutzuy
authors.initials: T
authors.lastname: Ramirez
authors.forename: Barbara
authors.initials: B
authors.lastname: Rothen-Rutishauser
authors.forename: Monika
authors.initials: M
authors.lastname: Schäfer-Korting
authors.forename: Katrin
authors.initials: K
authors.lastname: Zeilinger
authors.forename: Marie-Gabriele
authors.initials: MG
authors.lastname: Zurich
mesh_terms: D000826:Animal Testing Alternatives / Q000379:methods*; D000818:Animals; D001681:Biological Assay / Q000295:instrumentation / Q000379:methods; D018929:Cell Culture Techniques / Q000295:instrumentation* / Q000379:methods*; D056656:Lab-On-A-Chip Devices; D008954:Models, Biological