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Cell-Based Assays Using iPSCs for Drug Development and Testing pp 55–70Cite as

Production of Cardiomyocytes from Human Pluripotent Stem Cells by Bioreactor Technologies

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1994))

Abstract

Cardiomyocytes from human pluripotent stem cells (hPSCs) have the ability to advance specificity of in vitro assays for drug discovery and safety pharmacology. They may also provide a superior cell source for envisioned cell therapies to repair damaged hearts. All applications will require the production of cardiomyocytes (CMs) by robust upscalable bioprocesses via industry-compliant technologies. This paper describes a detailed procedure for producing hPSC-CMs in stirred tank bioreactors in 100 ml process scale. The strategy combines both hPSC expansion in suspension culture and, directly followed by, cardiogenic differentiation using small molecule-Wnt pathway modulators. We also provide a protocol describing how to plan and expand the pluripotent stem cells to enable parallel inoculation of 4× 150 ml parallel bioreactor differentiations, potentially producing more than 240 × 106 cardiomyocytes in 22 days.

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Acknowledgments

This work was supported by StemBANCC (support from the Innovative Medicines Initiative joint undertaking under grant 115439-2, whose resources are composed of financial contribution from the European Union [FP7/2007-2013] and EFPIA companies’ in-kind contribution). RZ received funding from the German Research Foundation (DFG; including the Cluster of Excellence REBIRTH EXC 62/2 and grants ZW64/4-1, KFO311, and ZW64/7-1), the German Ministry for Education and Science (BMBF; grants: 13N14086, 01EK1601A, and 01EK1602A) and by the European Union (TECHNOBEAT; grant 66724).

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Authors and Affiliations

  1. Leibniz Research Laboratories for Biotechnology and Artificial Organs (LEBAO), Department of Cardiac, Thoracic, Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany

    Caroline Halloin, Michelle Coffee, Felix Manstein & Robert Zweigerdt

  2. REBIRTH-Cluster of Excellence, Hannover Medical School, Hannover, Germany

    Caroline Halloin, Michelle Coffee, Felix Manstein & Robert Zweigerdt

Authors
  1. Caroline Halloin
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  2. Michelle Coffee
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  3. Felix Manstein
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  4. Robert Zweigerdt
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Corresponding author

Correspondence to Robert Zweigerdt .

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Editors and Affiliations

  1. Division of Biotechnology, Department of Physics, Chemistry and Biology (IFM), Linköping University, Linköping, Sweden

    Carl-Fredrik Mandenius

  2. Tissue Injury and Repair Group, University of Edinburgh, Edinburgh, UK

    James A. Ross

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Halloin, C., Coffee, M., Manstein, F., Zweigerdt, R. (2019). Production of Cardiomyocytes from Human Pluripotent Stem Cells by Bioreactor Technologies. In: Mandenius, CF., Ross, J. (eds) Cell-Based Assays Using iPSCs for Drug Development and Testing. Methods in Molecular Biology, vol 1994. Humana, New York, NY. https://doi.org/10.1007/978-1-4939-9477-9_5

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  • DOI: https://doi.org/10.1007/978-1-4939-9477-9_5

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  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-4939-9476-2

  • Online ISBN: 978-1-4939-9477-9

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