iPSC-Derived Macrophages Effectively Treat Pulmonary Alveolar Proteinosis in Csf2rb-Deficient Mice

Publication date: Available online 9 August 2018Source: Stem Cell ReportsAuthor(s): Adele Mucci, Elena Lopez-Rodriguez, Miriam Hetzel, Serena Liu, Takuji Suzuki, Christine Happle, Mania Ackermann, Henning Kempf, Roman Hillje, Jessica Kunkiel, Ewa Janosz, Sebastian Brennig, Silke Glage, Jens P. Bankstahl, Sabine Dettmer, Thomas Rodt, Gudrun Gohring, Bruce Trapnell, Gesine Hansen, Cole TrapnellSummaryInduced pluripotent stem cell (iPSC)-derived hematopoietic cells represent a highly attractive source for cell and gene therapy. Given the longevity, plasticity, and self-renewal potential of distinct macrophage subpopulations, iPSC-derived macrophages (iPSC-Mφ) appear of particular interest in this context. We here evaluated the airway residence, plasticity, and therapeutic efficacy of iPSC-Mφ in a murine model of hereditary pulmonary alveolar proteinosis (herPAP). We demonstrate that single pulmonary macrophage transplantation (PMT) of 2.5–4 × 106 iPSC-Mφ yields efficient airway residence with conversion of iPSC-Mφ to an alveolar macrophage (AMφ) phenotype characterized by a distinct surface marker and gene expression profile within 2 months. Moreover, PMT significantly improves alveolar protein deposition and other critical herPAP disease parameters. Thus, our data indicate iPSC-Mφ as a source of functional macrophages displaying substantial plasticity and therapeutic potential that upon pulmonary transplantation will integrate into the lung microenvironment, adopt an...
Source: Stem Cell Reports - Category: Stem Cells Source Type: research