title: 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.affiliation: Research Group Reprogramming and Gene Therapy, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, Germany; Junior Research Group Translational Hematology of Congenital Diseases, Cluster of Excellence REBIRTH, Hannover Medical School, Carl-Neuberg-Street 1, 30625 Hannover, Germany; Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Adele
authors.initials: A
authors.lastname: Mucci
authors.affiliation: Research Group Reprogramming and Gene Therapy, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, Germany; Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Jessica
authors.initials: J
authors.lastname: Kunkiel
authors.affiliation: Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Takuji
authors.initials: T
authors.lastname: Suzuki
authors.affiliation: Research Group Reprogramming and Gene Therapy, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, Germany; Junior Research Group Translational Hematology of Congenital Diseases, Cluster of Excellence REBIRTH, Hannover Medical School, Carl-Neuberg-Street 1, 30625 Hannover, Germany; Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Sebastian
authors.initials: S
authors.lastname: Brennig
authors.affiliation: Institute of Laboratory Animal Science and Central Animal Facility, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Glage
authors.affiliation: Department of Functional and Applied Anatomy, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Mark P
authors.initials: MP
authors.lastname: Kühnel
authors.affiliation: Research Group Reprogramming and Gene Therapy, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, Germany; Junior Research Group Translational Hematology of Congenital Diseases, Cluster of Excellence REBIRTH, Hannover Medical School, Carl-Neuberg-Street 1, 30625 Hannover, Germany; Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Mania
authors.initials: M
authors.lastname: Ackermann
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), 30625 Hannover, Germany.
authors.forename: Christine
authors.initials: C
authors.lastname: Happle
authors.affiliation: Research Group Reprogramming and Gene Therapy, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, Germany; Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Alexandra
authors.initials: A
authors.lastname: Kuhn
authors.affiliation: Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany; Division of Hematology/Oncology, Boston Children's Hospital, Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Axel
authors.initials: A
authors.lastname: Schambach
authors.affiliation: Translational Pulmonary Science Center, Cincinnati Children's Hospital Medical Center, Cincinnati, OH 45229, USA.
authors.forename: Bruce C
authors.initials: BC
authors.lastname: Trapnell
authors.affiliation: Department of Pediatric Pneumology, Allergology and Neonatology, Hannover Medical School, 30625 Hannover, Germany; Biomedical Research in Endstage and Obstructive Lung Disease Hannover (BREATH), Member of the German Center for Lung Research (DZL), 30625 Hannover, Germany.
authors.forename: Gesine
authors.initials: G
authors.lastname: Hansen
authors.affiliation: Research Group Reprogramming and Gene Therapy, Cluster of Excellence REBIRTH, Hannover Medical School, 30625 Hannover, Germany; Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Moritz
authors.affiliation: Junior Research Group Translational Hematology of Congenital Diseases, Cluster of Excellence REBIRTH, Hannover Medical School, Carl-Neuberg-Street 1, 30625 Hannover, Germany; Institute of Experimental Hematology, Hannover Medical School, 30625 Hannover, Germany. Electronic address: lachmann.nico@mh-hannover.de.
authors.forename: Nico
authors.initials: N
authors.lastname: Lachmann
mesh_terms: D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D053648:Cytokine Receptor Common beta Subunit / Q000172:deficiency* / Q000378:metabolism; D004195:Disease Models, Animal; D016178:Granulocyte-Macrophage Colony-Stimulating Factor / Q000494:pharmacology; D006410:Hematopoiesis / Q000187:drug effects; D057026:Induced Pluripotent Stem Cells / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D011649:Pulmonary Alveolar Proteinosis / Q000378:metabolism* / Q000473:pathology*
chemical_list: D015415:Biomarkers; D053648:Cytokine Receptor Common beta Subunit; C072186:Csf2rb protein, mouse; D016178:Granulocyte-Macrophage Colony-Stimulating Factor
keywords: PAP; disease modeling; hematopoiesis; iPSC; macrophages