Science and Research

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

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.
Publication details
DOI: 10.1038/s41467-018-07570-7
Journal: Nature communications
Pages: 5088 
Number: 1
Work Type: Original
Location: BREATH
Disease Area: PALI
Partner / Member: ITEM, MHH
Access-Number: 30504915
See publication on PubMed

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