2018
DOI: 10.1007/s00204-018-2152-9
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Innovative organotypic in vitro models for safety assessment: aligning with regulatory requirements and understanding models of the heart, skin, and liver as paradigms

Abstract: The development of improved, innovative models for the detection of toxicity of drugs, chemicals, or chemicals in cosmetics is crucial to efficiently bring new products safely to market in a cost-effective and timely manner. In addition, improvement in models to detect toxicity may reduce the incidence of unexpected post-marketing toxicity and reduce or eliminate the need for animal testing. The safety of novel products of the pharmaceutical, chemical, or cosmetics industry must be assured; therefore, toxicolo… Show more

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Cited by 38 publications
(25 citation statements)
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References 85 publications
(90 reference statements)
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“…Integration of PHH spheroids into microfluidic chips is therefore considered a promising avenue in which the microenvironment can be more tightly regulated and potential interactions with other organs can be generated. It is anticipated that such organotypic in vitro models will increase our understanding of human bodily functions, are of value for disease modelling and screening of novel therapeutic interventions, and may aid in enhancing safety assessments in drug development (337)(338)(339)(340).…”
Section: General Discussion and Future Perspectivesmentioning
confidence: 99%
“…Integration of PHH spheroids into microfluidic chips is therefore considered a promising avenue in which the microenvironment can be more tightly regulated and potential interactions with other organs can be generated. It is anticipated that such organotypic in vitro models will increase our understanding of human bodily functions, are of value for disease modelling and screening of novel therapeutic interventions, and may aid in enhancing safety assessments in drug development (337)(338)(339)(340).…”
Section: General Discussion and Future Perspectivesmentioning
confidence: 99%
“…Moreover, this methodology is strictly quantitative requiring the integration of quantitative data and modelling to develop mechanistic knowledge of the system and reveal pharmacological and toxicological properties. Consequently, systems pharmacology models are becoming an increasingly important part of the toolkit to improve capabilities and drive innovation for in vitro safety assessment [10][11][12].…”
Section: Introductionmentioning
confidence: 99%
“…Two of the most promising areas of research for novel in vitro hepatic co-culture models are 3D spheroids/microtissues and flow-based microphysiological systems (MPS) (Esch et al 2015;Ewart et al 2018;Pridgeon et al 2018;Whitman et al 2016;Williams et al 2013). Both have demonstrated superior enzyme expression or functionality of phase I and II, and transporter proteins over simple 2D cultures in extended culture periods (Bell et al 2018;Tsamandouras et al 2017).…”
Section: Introductionmentioning
confidence: 99%