Journal
NATURE COMMUNICATIONS
Volume 9, Issue -, Pages -Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/s41467-018-07570-7
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Funding
- Deutsche Forschungsgemeinschaft [Exc 62/1, DFG LA 3680/2-1, ZW64/4-1]
- Else-Kroner-Fresenius-Stiftung [EKFS 2013_A24, 2015_A92, 2016_A146]
- German Ministry for Education and Science (BMBF) [13N12606, 13N14086, 01EK1602A]
- European Union [FP7/2007-2013] [115439-2]
- TECHNOBEAT (European Union H2020) [668724]
- Joachim Herz Stiftung
- MHH Hannover (HiLF grant)
- [SFB738]
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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.
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