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.
- Ackermann, M.
- Kempf, H.
- Hetzel, M.
- Hesse, C.
- Hashtchin, A. R.
- Brinkert, K.
- Schott, J. W.
- Haake, K.
- Kuhnel, M. P.
- Glage, S.
- Figueiredo, C.
- Jonigk, D.
- Sewald, K.
- Schambach, A.
- Wronski, S.
- Moritz, T.
- Martin, U.
- Zweigerdt, R.
- Munder, A.
- Lachmann, N.
