Science and Research

Murine iPSC-Derived Macrophages as a Tool for Disease Modeling of Hereditary Pulmonary Alveolar Proteinosis due to Csf2rb Deficiency

Induced pluripotent stem cells (iPSCs) represent an innovative source for the standardized in vitro generation of macrophages (Mphi). We here describe a robust and efficient protocol to obtain mature and functional Mphi from healthy as well as disease-specific murine iPSCs. With regard to morphology, surface phenotype, and function, our iPSC-derived Mphi (iPSC-Mphi) closely resemble their counterparts generated in vitro from bone marrow cells. Moreover, when we investigated the feasibility of our differentiation system to serve as a model for rare congenital diseases associated with Mphi malfunction, we were able to faithfully recapitulate the pathognomonic defects in GM-CSF signaling and Mphi function present in hereditary pulmonary alveolar proteinosis (herPAP). Thus, our studies may help to overcome the limitations placed on research into certain rare disease entities by the lack of an adequate supply of disease-specific primary cells, and may aid the development of novel therapeutic approaches for herPAP patients.

  • Mucci, A.; Kunkiel, J.; Suzuki, T.; Brennig, S.; Glage, S.; Kuhnel, M. P.; Ackermann, M.; Happle, C.; Kuhn, A.; Schambach, A.; Trapnell, B. C.; Hansen, G.; Moritz, T.; Lachmann, N.

Keywords

  • Pap
  • disease modeling
  • hematopoiesis
  • iPSC
  • macrophages
Publication details
DOI: 10.1016/j.stemcr.2016.06.011
Journal: Stem cell reports
Pages: 292-305 
Number: 2
Work Type: Original
Location: BREATH
Disease Area: ROR
Partner / Member: MHH
Access-Number: 27453007
See publication on PubMed

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