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A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device
Linköping University, Department of Physics, Chemistry and Biology, Biotechnology. Linköping University, Faculty of Science & Engineering.ORCID iD: 0000-0001-5914-2837
Boehringer Ingelheim Pharma GmbH and Co. KG, Nonclinical Drug Safety Germany, D-88397 Biberach an der Riss, Germany.
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany.
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2018 (English)In: Bioengineering, E-ISSN 2306-5354, Vol. 5, no 2, p. 1-13, article id 36Article in journal (Refereed) Published
Abstract [en]

Three-dimensional (3D) models with cells arranged in clusters or spheroids have emerged as valuable tools to improve physiological relevance in drug screening. One of the challenges with cells cultured in 3D, especially for high-throughput applications, is to quickly and non-invasively assess the cellular state in vitro. In this article, we show that the number of cells growing out from human induced pluripotent stem cell (hiPSC)-derived cardiac spheroids can be quantified to serve as an indicator of a drug’s effect on spheroids captured in a microfluidic device. Combining this spheroid-on-a-chip with confocal high content imaging reveals easily accessible, quantitative outgrowth data. We found that effects on outgrowing cell numbers correlate to the concentrations of relevant pharmacological compounds and could thus serve as a practical readout to monitor drug effects. Here, we demonstrate the potential of this semi-high-throughput “cardiac cell outgrowth assay” with six compounds at three concentrations applied to spheroids for 48 h. The image-based readout complements end-point assays or may be used as a non-invasive assay for quality control during long-term culture.

Place, publisher, year, edition, pages
2018. Vol. 5, no 2, p. 1-13, article id 36
National Category
Cell and Molecular Biology Biomedical Laboratory Science/Technology Medical Biotechnology (with a focus on Cell Biology (including Stem Cell Biology), Molecular Biology, Microbiology, Biochemistry or Biopharmacy)
Identifiers
URN: urn:nbn:se:liu:diva-154007DOI: 10.3390/bioengineering5020036OAI: oai:DiVA.org:liu-154007DiVA, id: diva2:1281361
Available from: 2019-01-22 Created: 2019-01-22 Last updated: 2019-03-29Bibliographically approved
In thesis
1. Organs-on-chips for the pharmaceutical development process: design perspectives and implementations
Open this publication in new window or tab >>Organs-on-chips for the pharmaceutical development process: design perspectives and implementations
2018 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Organs-on-chips are dynamic cell culture devices created with the intention to mimic organ function in vitro. Their purpose is to assess the toxicity and efficacy of drugs and, as early as possible in the pharmaceutical development process, predict the outcome of clinical trials. The aim of this thesis is to explain and discuss these cell culture devices from a design perspective and to experimentally exemplify some of the specific functions that characterize organs-on-chips.

The cells in our body reside in complex environments with chemical and mechanical cues that affect their function and purpose. Such a complex environment is difficult to recreate in the laboratory and has therefore been overlooked in favor of more simple models, i.e. static twodimensional (2D) cell cultures. Numerous recent reports have shown cell culture systems that can resemble the cell’s natural habitat and enhance cell functionality and thereby potentially provide results that better reflects animal and human trials. The way these organs-on-chips improve in vitro cell culture assays is to include e.g. a three-dimensional cell architecture (3D), mechanical stimuli, gradients of oxygen or nutrients, or by combining several relevant cell types that affect each other in close proximity.

The research conducted for this thesis shows how cells in 3D spheroids or in 3D hydrogels can be cultured in perfused microbioreactors. Furthermore, a pump based on electroosmosis, and a method for an objective conceptual design process, is introduced to the field of organs-on-chips.

Place, publisher, year, edition, pages
Linköping: Linköping University Electronic Press, 2018. p. 78
Series
Linköping Studies in Science and Technology. Dissertations, ISSN 0345-7524 ; 1907
Keywords
Organs-on-chips, cell culture models, pharmaceutical development, microfluidics
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:liu:diva-145300 (URN)10.3384/diss.diva-145300 (DOI)9789176853597 (ISBN)
Public defence
2018-03-23, Planck, Fysikhuset, Campus Valla, Linköping, 13:30 (English)
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Note

I den tryckta versionen är det ena serienamnet felaktigt. I den elektroniska versionen är detta ändrat till korrekt "Linköping Studies in Science and Technology. Dissertations"

Available from: 2018-02-21 Created: 2018-02-21 Last updated: 2019-09-26Bibliographically approved

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