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

: 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

Volltext urn:nbn:de:0011-n-5376833 (2.7 MByte PDF)
MD5 Fingerprint: 8012825126611d4f0637a8a450663d96
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Erstellt am: 26.3.2019

Nature Communications 9 (2018), Art. 5088, 13 S.
ISSN: 2041-1723
Zeitschriftenaufsatz, Elektronische Publikation
Fraunhofer ITEM ()

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.