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

Nat Commun. 2018 Nov 30;9(1):5088. doi: 10.1038/s41467-018-07570-7.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bacterial Infections / immunology
  • Bacterial Infections / prevention & control*
  • Bioreactors*
  • Cell Culture Techniques
  • Humans
  • Immunotherapy / methods*
  • Induced Pluripotent Stem Cells / cytology*
  • Macrophages / cytology*
  • Macrophages / physiology
  • Mice
  • Microscopy, Electron, Scanning
  • Pseudomonas aeruginosa / pathogenicity
  • Respiratory Tract Infections / immunology
  • Respiratory Tract Infections / prevention & control*