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Bioengineering (Basel). 2018 May 4;5(2). pii: E36. doi: 10.3390/bioengineering5020036.

A Cardiac Cell Outgrowth Assay for Evaluating Drug Compounds Using a Cardiac Spheroid-on-a-Chip Device.

Author information

1
Division of Biotechnology, Department of Physics, Chemistry and Biology (IFM), Linköping University, 58183 Linköping, Sweden. jonas.christoffersson@liu.se.
2
Boehringer Ingelheim Pharma GmbH and Co. KG, Nonclinical Drug Safety Germany, D-88397 Biberach an der Riss, Germany. florian.meier@boehringer-ingelheim.com.
3
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Kempf.Henning@mh-hannover.de.
4
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Schwanke.Kristin@mh-hannover.de.
5
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Coffee.Michelle@mh-hannover.de.
6
Boehringer Ingelheim Pharma GmbH and Co. KG, Nonclinical Drug Safety Germany, D-88397 Biberach an der Riss, Germany. mario.beilmann@boehringer-ingelheim.com.
7
Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Hannover Medical School, Carl-Neuberg-Str. 1, 30625 Hannover, Germany. Zweigerdt.Robert@mh-hannover.de.
8
Division of Biotechnology, Department of Physics, Chemistry and Biology (IFM), Linköping University, 58183 Linköping, Sweden. carl-fredrik.mandenius@liu.se.

Abstract

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.

KEYWORDS:

3D cell culture; cardiac spheroids; cardiomyocytes; drug screening; induced pluripotent stem cells (iPSCs); microfluidics; organ-on-a-chip

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