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

Abstract

Induced pluripotent stem cells (iPSCs) represent an innovative source for the standardized in vitro generation of macrophages (Mφ). We here describe a robust and efficient protocol to obtain mature and functional Mφ from healthy as well as disease-specific murine iPSCs. With regard to morphology, surface phenotype, and function, our iPSC-derived Mφ (iPSC-Mφ) 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 Mφ malfunction, we were able to faithfully recapitulate the pathognomonic defects in GM-CSF signaling and Mφ 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.

• Authors: Adele Mucci, Jessica Kunkiel, Takuji Suzuki, Sebastian Brennig, Silke Glage, Mark P Kühnel, Mania Ackermann, Christine Happle, Alexandra Kuhn, Axel Schambach, Bruce C Trapnell, Gesine Hansen, Thomas Moritz, Nico Lachmann
• Journal: Stem cell reports (Stem Cell Reports) Vol. 7 Issue 2 Pg. 292-305 (08 09 2016) ISSN: 2213-6711 [Electronic] United States
• PMID: 27453007 (Publication Type: Journal Article)
• Copyright: Copyright © 2016 The Author(s). Published by Elsevier Inc. All rights reserved.

Chemical References

• Biomarkers
• Cytokine Receptor Common beta Subunit
• Csf2rb protein, mouse
• Granulocyte-Macrophage Colony-Stimulating Factor

Topics

• Animals
• Biomarkers (metabolism)
• Cell Differentiation (drug effects)
• Cytokine Receptor Common beta Subunit (deficiency, metabolism)
• Disease Models, Animal
• Granulocyte-Macrophage Colony-Stimulating Factor (pharmacology)
• Hematopoiesis (drug effects)
• Induced Pluripotent Stem Cells (cytology, drug effects, metabolism)
• Macrophages (cytology, drug effects, metabolism)
• Mice, Inbred C57BL
• Monocytes (drug effects, metabolism)
• Pulmonary Alveolar Proteinosis (metabolism, pathology)