CC BY 4.0Ackermann, ManiaManiaAckermannKempf, HenningHenningKempfHetzel, MiriamMiriamHetzelHesse, ChristinaChristinaHesseHashtchin, Anna RafieiAnna RafieiHashtchinBrinkert, KerstinKerstinBrinkertSchott, Juliane WilhelmineJuliane WilhelmineSchottHaake, KathrinKathrinHaakeKühnel, Mark PhilippMark PhilippKühnelGlage, SilkeSilkeGlageFigueiredo, ConstancaConstancaFigueiredoJonigk, DannyDannyJonigkSewald, KatherinaKatherinaSewaldSchambach, AxelAxelSchambachWronski, SabineSabineWronskiMoritz, ThomasThomasMoritzMartin, UlrichUlrichMartinZweigerdt, RobertRobertZweigerdtMunder, AntjeAntjeMunderLachmann, NicoNicoLachmann2022-03-0526.3.20192018https://publica.fraunhofer.de/handle/publica/25704210.1038/s41467-018-07570-710.24406/publica-r-257042The 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.en610620journal article