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  4. Bioreactor-based mass production of human iPSC-derived macrophages enables immunotherapies against bacterial airway infections
 
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2018
Journal Article
Title

Bioreactor-based mass production of human iPSC-derived macrophages enables immunotherapies against bacterial airway infections

Abstract
The increasing number of severe infections with multi-drug-resistant pathogens worldwide highlights the need for alternative treatment options. Given the pivotal role of phagocytes and especially alveolar macrophages in pulmonary immunity, we introduce a new, cell-based treatment strategy to target bacterial airway infections. Here we show that the mass production of therapeutic phagocytes from induced pluripotent stem cells (iPSC) in industry-compatible, stirred-tank bioreactors is feasible. Bioreactor-derived iPSC-macrophages (iPSC-Mac) represent a highly pure population of CD45(+)CD11b(+)CD14(+)CD163(+) cells, and share important phenotypic, functional and transcriptional hallmarks with professional phagocytes, however with a distinct transcriptome signature similar to primitive macrophages. Most importantly, bioreactor-derived iPSC-Mac rescue mice from Pseudomonas aeruginosa-mediated acute infections of the lower respiratory tract within 4-8 h post intra-pulmonary transplantation and reduce bacterial load. Generation of specific immune-cells from iPSC-sources in scalable stirred-tank bioreactors can extend the field of immunotherapy towards bacterial infections, and may allow for further innovative cell-based treatment strategies.
Author(s)
Ackermann, Mania
Kempf, Henning
Hetzel, Miriam
Hesse, Christina  
Hashtchin, Anna Rafiei
Brinkert, Kerstin
Schott, Juliane Wilhelmine
Haake, Kathrin
Kühnel, Mark Philipp
Glage, Silke
Figueiredo, Constanca
Jonigk, Danny
Sewald, Katherina  
Schambach, Axel
Wronski, Sabine  
Moritz, Thomas
Martin, Ulrich
Zweigerdt, Robert
Munder, Antje
Lachmann, Nico
Journal
Nature Communications  
Open Access
File(s)
Download (2.71 MB)
Rights
CC BY 4.0: Creative Commons Attribution
DOI
10.24406/publica-r-257042
10.1038/s41467-018-07570-7
Language
English
Fraunhofer-Institut für Toxikologie und Experimentelle Medizin ITEM  
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