Abstract
The recent advent of microphysiological systems - microfluidic biomimetic devices that aspire to emulate the biology of human tissues, organs and circulation in vitro - is envisaged to enable a global paradigm shift in drug development. An extraordinary US governmental initiative and various dedicated research programs in Europe and Asia have led recently to the first cutting-edge achievements of human single-organ and multi-organ engineering based on microphysiological systems. The expectation is that test systems established on this basis would model various disease stages, and predict toxicity, immunogenicity, ADME profiles and treatment efficacy prior to clinical testing. Consequently, this technology could significantly affect the way drug substances are developed in the future. Furthermore, microphysiological system-based assays may revolutionize our current global programs of prioritization of hazard characterization for any new substances to be used, for example, in agriculture, food, ecosystems or cosmetics, thus, replacing laboratory animal models used currently. Thirty-six experts from academia, industry and regulatory bodies present here the results of an intensive workshop (held in June 2015, Berlin, Germany). They review the status quo of microphysiological systems available today against industry needs, and assess the broad variety of approaches with fit-for-purpose potential in the drug development cycle. Feasible technical solutions to reach the next levels of human biology in vitro are proposed. Furthermore, key organ-on-a-chip case studies, as well as various national and international programs are highlighted. Finally, a roadmap into the future is outlined, to allow for more predictive and regulatory-accepted substance testing on a global scale.
Highlights
The findings further demonstrate that the use of well formats with an already labor-intensive pipetting protocol cannot reproduce the results obtained with continuous media exchange, as has been exemplified for a setup including only two different tissue types
The results suggest that ifosfamide nephrotoxicity in a liver-kidney microfluidic co-culture model using HepaRG-MDCK cells is induced by the metabolism of ifosfamide into chloroacetaldehyde
The respective toxicological endpoints are challenging to address in vivo as well as in vitro, and it is in this context that microphysiological in vitro systems (MPS) would ideally put their strength to the test, especially since they allow the breakdown of the species barrier by using human cells
Summary
According to the most recent report from the European Commission (EC) to the Council and the European Parliament (EC, 2013), 11.5 million animals were used for experimental and other scientific purposes in the Member States of the European Union (EU) in 2011. 2.3.2 State of the art of microphysiological single-organ systems Early microtiter plate-based microfluidic cell culture formats with passive gravity-based microfluidic flow approaches to in vitro tissue regeneration with application in human disease modeling and drug development were developed by CellAsic (Lee et al, 2007a). The important features of adjustable flow rates on the basis of an oxygen consumption model, long-term steady gradient maintenance and the amenability to co-culture of hepatocytes with different types of non-parenchymal cells made the system an interesting approach for toxicity testing It is one of the still rare cases where a research MPS has been transferred into industrial application. Value-adding MPS-based tools and approaches, once qualified, can immediately be used for internal decision-making in product development
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