title: 'Human-on-a-chip' developments: a translational cutting-edge alternative to systemic safety assessment and efficiency evaluation of substances in laboratory animals and man?
abstract: Various factors, including the phylogenetic distance between laboratory animals and humans, the discrepancy between current in vitro systems and the human body, and the restrictions of in silico modelling, have generated the need for new solutions to the ever-increasing worldwide dilemma of substance testing. This review provides a historical sketch on the accentuation of this dilemma, and highlights fundamental limitations to the countermeasures taken so far. It describes the potential of recently-introduced microsystems to emulate human organs in 'organ-on-a-chip' devices. Finally, it focuses on an in-depth analysis of the first devices that aimed to mimic human systemic organ interactions in 'human-on-a-chip' systems. Their potential to replace acute systemic toxicity testing in animals, and their inability to provide alternatives to repeated dose long-term testing, are discussed. Inspired by the latest discoveries in human biology, tissue engineering and micro-systems technology, this review proposes a paradigm shift to overcome the apparent challenges. A roadmap is outlined to create a new homeostatic level of biology in 'human-on-a-chip' systems in order to, in the long run, replace systemic repeated dose safety evaluation and disease modelling in animals.
authors.affiliation: Technische Universität Berlin, Department of Biotechnology, Berlin, Germany. uwe.marx@tu-berlin.de
authors.forename: Uwe
authors.initials: U
authors.lastname: Marx
authors.forename: Heike
authors.initials: H
authors.lastname: Walles
authors.forename: Silke
authors.initials: S
authors.lastname: Hoffmann
authors.forename: Gerd
authors.initials: G
authors.lastname: Lindner
authors.forename: Reyk
authors.initials: R
authors.lastname: Horland
authors.forename: Frank
authors.initials: F
authors.lastname: Sonntag
authors.forename: Udo
authors.initials: U
authors.lastname: Klotzbach
authors.forename: Dmitry
authors.initials: D
authors.lastname: Sakharov
authors.forename: Alexander
authors.initials: A
authors.lastname: Tonevitsky
authors.forename: Roland
authors.initials: R
authors.lastname: Lauster
mesh_terms: D000826:Animal Testing Alternatives; D000818:Animals; D000830:Animals, Laboratory; D006801:Humans; D046210:Microfluidic Analytical Techniques / Q000379:methods*; D057905:Stem Cell Research; D018675:Toxicity Tests / Q000379:methods*