Journal article
Large-scale production of human iPSC-derived macrophages for drug screening
- Abstract:
- 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.
- Publication status:
- Published
- Peer review status:
- Peer reviewed
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(Preview, Version of record, pdf, 6.2MB, Terms of use)
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- Publisher copy:
- 10.3390/ijms21134808
Authors
- Publisher:
- MDPI
- Journal:
- International Journal of Molecular Sciences More from this journal
- Volume:
- 21
- Issue:
- 13
- Article number:
- 4808
- Publication date:
- 2020-07-07
- Acceptance date:
- 2020-07-03
- DOI:
- EISSN:
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1422-0067
- ISSN:
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1422-0067
- Pmid:
-
32645954
- Language:
-
English
- Keywords:
- Pubs id:
-
1119392
- Local pid:
-
pubs:1119392
- Deposit date:
-
2020-08-20
- ARK identifier:
Terms of use
- Copyright holder:
- Gutbier et al.
- Copyright date:
- 2020
- Rights statement:
- ©2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open accessarticle distributed under the terms and conditions of the Creative Commons Attribution(CC BY) license (http://creativecommons.org/licenses/by/4.0/).
- Licence:
- CC Attribution (CC BY)
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