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

Mania Ackermann, Henning Kempf, Miriam Hetzel, Christina Hesse, Anna Rafiei Hashtchin, Kerstin Brinkert, Juliane Wilhelmine Schott, Kathrin Haake, Mark Philipp Kühnel, Silke Glage, Constanca Figueiredo, Danny Jonigk, Katherina Sewald, Axel Schambach, Sabine Wronski, Thomas Moritz, Ulrich Martin, Robert Zweigerdt, Antje Munder and Nico Lachmann ()
Additional contact information
Mania Ackermann: Hannover Medical School
Henning Kempf: Hannover Medical School
Miriam Hetzel: Hannover Medical School
Christina Hesse: REBIRTH Cluster-of Excellence
Anna Rafiei Hashtchin: Hannover Medical School
Kerstin Brinkert: Hannover Medical School
Juliane Wilhelmine Schott: Hannover Medical School
Kathrin Haake: Hannover Medical School
Mark Philipp Kühnel: German Center for Lung Research
Silke Glage: Hannover Medical School
Constanca Figueiredo: Hannover Medical School
Danny Jonigk: German Center for Lung Research
Katherina Sewald: REBIRTH Cluster-of Excellence
Axel Schambach: Hannover Medical School
Sabine Wronski: REBIRTH Cluster-of Excellence
Thomas Moritz: Hannover Medical School
Ulrich Martin: Hannover Medical School
Robert Zweigerdt: Hannover Medical School
Antje Munder: German Center for Lung Research
Nico Lachmann: Hannover Medical School

Nature Communications, 2018, vol. 9, issue 1, 1-13

Abstract: 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.

Date: 2018
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DOI: 10.1038/s41467-018-07570-7

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