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Open AccessArticle

Large-Scale Production of Human iPSC-Derived Macrophages for Drug Screening

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Roche Pharma Research and Early Development, Therapeutic Modalities, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland
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Roche Pharma Research and Early Development, Pharmaceutical Sciences, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland
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Roche Pharma Research and Early Development, Neuroscience and Rare Diseases Discovery and Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland
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Roche Pharma Research and Early Development, Immunology and Infectious Diseases Discovery and Translational Area, Roche Innovation Center Basel, F. Hoffmann-La Roche Ltd., Grenzacherstrasse 124, 4070 Basel, Switzerland
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James Martin Stem Cell Facility, Sir William Dunn School of Pathology, University of Oxford, Oxford OX1 3RE, UK
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BlueRock Therapeutics, New York, NY 10016, USA
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(13), 4808; https://doi.org/10.3390/ijms21134808
Received: 5 June 2020 / Revised: 2 July 2020 / Accepted: 3 July 2020 / Published: 7 July 2020
(This article belongs to the Special Issue Disease Modeling Using Human Induced Pluripotent Stem Cells 2.0)
Tissue-resident macrophages are key players in inflammatory processes, and their activation and functionality are crucial in health and disease. Numerous diseases are associated with alterations in homeostasis or dysregulation of the innate immune system, including allergic reactions, autoimmune diseases, and cancer. Macrophages are a prime target for drug discovery due to their major regulatory role in health and disease. Currently, the main sources of macrophages used for therapeutic compound screening are primary cells isolated from blood or tissue or immortalized or neoplastic cell lines (e.g., THP-1). Here, we describe an improved method to employ induced pluripotent stem cells (iPSCs) for the high-yield, large-scale production of cells resembling tissue-resident macrophages. For this, iPSC-derived macrophage-like cells are thoroughly characterized to confirm their cell identity and thus their suitability for drug screening purposes. These iPSC-derived macrophages show strong cellular identity with primary macrophages and recapitulate key functional characteristics, including cytokine release, phagocytosis, and chemotaxis. Furthermore, we demonstrate that genetic modifications can be readily introduced at the macrophage-like progenitor stage in order to interrogate drug target-relevant pathways. In summary, this novel method overcomes previous shortcomings with primary and leukemic cells and facilitates large-scale production of genetically modified iPSC-derived macrophages for drug screening applications. View Full-Text
Keywords: myeloid cells; primitive macrophages; induced pluripotent stem cells; in vitro characterization; drug discovery; disease modeling myeloid cells; primitive macrophages; induced pluripotent stem cells; in vitro characterization; drug discovery; disease modeling
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Gutbier, S.; Wanke, F.; Dahm, N.; Rümmelin, A.; Zimmermann, S.; Christensen, K.; Köchl, F.; Rautanen, A.; Hatje, K.; Geering, B.; Zhang, J.D.; Britschgi, M.; Cowley, S.A.; Patsch, C. Large-Scale Production of Human iPSC-Derived Macrophages for Drug Screening. Int. J. Mol. Sci. 2020, 21, 4808.

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