Biology-inspired microphysiological systems to advance medicines for patient benefit and animal welfare

Marx, Uwe; Akabane, T; Andersson, T.; Baker, Elizabeth; Beilmann, Mario; Beken, Sonja; Brendler‐Schwaab, Susanne; Cirit, Murat; David, Rachel; Dehne, Eva-Maria; Durieux, Isabell; Ewart, Lorna; Sc, Fitzpatrick; Frey, Olivier; Fuchs, Florian; Lg, Griffith; Ga, Hamilton; Hartung, Thomas; Hoeng, Julia; Högberg, Helena T.; Dj, Hughes; De, Ingber; Iskandar, Anita; Kanamori, Toshiyuki; Kojima, Hajime; Kuehnl, Jochen; Leist, Marcel; B, Li; Loskill, Peter; Dl, Mendrick; Neumann, Thomas; Pallocca, Giorgia; Rusyn, Ivan; Smirnova, Lena; Steger‐Hartmann, Thomas; Da, Tagle; Tonevitsky, Alexander G.; Tsyb, Sergej; Trapečar, Martin; B, Van de Water; J, Van den Eijnden-van Raaij; Vulto, Paul; Watanabe, K.; Wolf, Armin; Zhou, Xiaobing; Roth, Adrian

doi:10.14573/altex.2001241

Cited by 141 publications

(165 citation statements)

References 78 publications

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“…The other common response is to breed or genetically modify lab animals such as mice to render them susceptible, as was done for the earlier SARS virus (McCray et al 2007). However, this misses the most obvious opportunity: human microphysiological systems (MPS) that have become available over the last decade due to stem cell technology and bioengineering (Alepee et al 2014;Marx et al 2016Marx et al , 2020Ewart et al 2018). We have shown earlier how viral infections can be studied in human BrainSpheres ("mini-brains") (Abreu et al 2018) for Zika and Dengue, as well as with others, including SARS-2-COVID-19 (to be published shortly).…”

Section: Drug Developmentmentioning

confidence: 99%

Harnessing the power of novel animal-free test methods for the development of COVID-19 drugs and vaccines

et al. 2020

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The COVID-19-inducing virus, SARS-CoV2, is likely to remain a threat to human health unless efficient drugs or vaccines become available. Given the extent of the current pandemic (people in over one hundred countries infected) and its disastrous effect on world economy (associated with limitations of human rights), speedy drug discovery is critical. In this situation, past investments into the development of new (animal-free) approach methods (NAM) for drug safety, efficacy, and quality evaluation can be leveraged. For this, we provide an overview of repurposing ideas to shortcut drug development times. Animal-based testing would be too lengthy, and it largely fails, when a pathogen is species-specific or if the desired drug is based on specific features of human biology. Fortunately, industry has already largely shifted to NAM, and some public funding programs have advanced the development of animal-free technologies. For instance, NAM can predict genotoxicity (a major aspect of carcinogenicity) within days, human antibodies targeting virus epitopes can be generated in molecular biology laboratories within weeks, and various human cell-based organoids are available to test virus infectivity and the biological processes controlling them. The European Medicines Agency (EMA) has formed an expert group to pave the way for the use of such approaches for accelerated drug development. This situation illustrates the importance of diversification in drug discovery strategies and clearly shows the shortcomings of an approach that invests 95% of resources into a single technology (animal experimentation) in the face of challenges that require alternative approaches.

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Section: Drug Developmentmentioning

confidence: 99%

Harnessing the power of novel animal-free test methods for the development of COVID-19 drugs and vaccines

et al. 2020

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“…OoC is a microfluidic-based device enabling to culture and grow living cells and organoid substructures in a controlled micro-environment. Commonly, OoC platforms recapitulate one or more aspects of the organ's dynamics, functionality, and in vivo (patho) physiological responses under real-time monitoring of different cultured tissue types [22]. The OoC technology has been developed, aiming for better prediction of the preclinical drug testing and reduction of the use of animal for the pharmaceutical industry [23,24].…”

Section: Introductionmentioning

confidence: 99%

Pancreas-on-a-Chip Technology for Transplantation Applications

et al. 2020

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Purpose of Review Human pancreas-on-a-chip (PoC) technology is quickly advancing as a platform for complex in vitro modeling of islet physiology. This review summarizes the current progress and evaluates the possibility of using this technology for clinical islet transplantation. Recent Findings PoC microfluidic platforms have mainly shown proof of principle for long-term culturing of islets to study islet function in a standardized format. Advancement in microfluidic design by using imaging-compatible biomaterials and biosensor technology might provide a novel future tool for predicting islet transplantation outcome. Progress in combining islets with other tissue types gives a possibility to study diabetic interventions in a minimal equivalent in vitro environment. Summary Although the field of PoC is still in its infancy, considerable progress in the development of functional systems has brought the technology on the verge of a general applicable tool that may be used to study islet quality and to replace animal testing in the development of diabetes interventions.

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“…Microphysiological systems (MPSs) [1][2][3] or Organ/Body-on-a-Chip (O/BoC) systems [4][5][6][7] hold great potential for application in drug development and toxicological testing. These platforms recapitulate physiological and pathological conditions in vivo in a chip without the use of actual organs, as an alternative to animal testing.…”

Section: Introductionmentioning

confidence: 99%

“…These platforms recapitulate physiological and pathological conditions in vivo in a chip without the use of actual organs, as an alternative to animal testing. 2,3 Most MPS are based on microfluidic technology, since it offers several benefits over the conventional macroscopic cell culture settings, such as precise liquid control, designed extracellular geometry, cellular positioning, and culturing in two-and three-dimensional fashions, which are very important for mimicking in vivo organ structures. 8,9 However, there is a critical issue to be solved.…”

Section: Introductionmentioning

confidence: 99%

Cyclo olefin polymer-based solvent-free mass-productive microphysiological systems

Yamanaka

Wen

Imamura

et al. 2020

Preprint

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A microphysiological system (MPS) holds a great promise for drug screening and toxicological testing as an alternative to animal models. However, this platform has several issues in terms of the materials used (e.g., polydimethylsiloxane), such as the absorbance of tested drug candidates and fluorescent dyes by the material, as well as the effect on cultured cellular status, thus misleading the results obtained from cell assays and fabrication processes. Hence, to eliminate the issues mentioned above, we developed a cyclo olefin polymer (COP)-based MPS via photobonding process using vacuum ultraviolet (VUV), named COP-VUV-MPS. COP-VUV-MPS showed better chemical resistance and avoided molecule absorption. COP-VUV-MPS could maintain the stemness of environmentally sensitive human-induced pluripotent stem cells without causing undesired cellular phenotypes and gene expression. These results suggested that COP-VUV-MPS might be broadly used for the advancement of MPS and applications in drug development and in vitro toxicological testing.

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Biology-inspired microphysiological systems to advance medicines for patient benefit and animal welfare

Cited by 141 publications

References 78 publications

Harnessing the power of novel animal-free test methods for the development of COVID-19 drugs and vaccines

Harnessing the power of novel animal-free test methods for the development of COVID-19 drugs and vaccines

Pancreas-on-a-Chip Technology for Transplantation Applications

Cyclo olefin polymer-based solvent-free mass-productive microphysiological systems

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