Prospectively defined murine mesenchymal stem cells inhibit Klebsiella pneumoniae-induced acute lung injury and improve pneumonia survival

• DOI: 10.1186/s12931-015-0288-1
• Publication Date: 2015-10-05T23:41:53Z
• Authors: Holger Hackstein; Anne Lippitsch; Philipp Krug; Inna Schevtschenko; Sabine Kranz; Matthias Hecker; Kristina Dietert; Achim D. Gruber; Gregor Bein; Cornelia Brendel; Nelli Baal
• Keywords: Pulmonary and Respiratory Medicine; CD4-Positive T-Lymphocytes; 0301 basic medicine; Time Factors; Acute Lung Injury; Cell Separation; Mesenchymal Stem Cell Transplantation; 03 medical and health sciences; Pneumonia, Bacterial; Animals; pneumonia; ddc:610; Lung; Klebsiella pneumonia; Cells, Cultured; mesenchymal stem cells; ddc:610; Research; Mesenchymal Stem Cells; Dendritic Cells; Flow Cytometry; Medical sciences Medicine; Klebsiella Infections; 3. Good health; Mice, Inbred C57BL; Disease Models, Animal; Klebsiella pneumoniae; Phenotype; acute lung injury; Feasibility Studies; Inflammation Mediators; Biomarkers

Numerous studies have described the immunosuppressive capacity of mesenchymal stem cells (MSC) but these use mixtures heterogeneous progenitor for in vitro expansion. Recently, multipotent MSC been prospectively identified murine bone marrow (BM) on basis PDFGRa+ SCA1+ CD45− TER119− (PαS) expression immunomodulatory is unknown. We isolated PαS by high-purity FACS sorting BM and after expansion we analyzed vivo activity during acute pneumonia. (1 × 106) were applied intratracheally 4 h respiratory Klebsiella pneumoniae induced infection. treatment resulted significantly reduced alveolitis protein leakage comparison to mock-treated controls. MSC-treated mice exhibited alveolar TNF-α IL-12p70 expression, while IL-10 was unaffected. Dissection dendritic cell (DC) subsets multiparameter flow cytometry revealed lung DC infiltration CD86 costimulatory CD103+ mice. In post-acute phase pneumonia, animals IL-17+ CD4+ T IFN-γ+ cells. Moreover, improved overall pneumonia survival did not increase bacterial load. this study demonstrated first time feasibility defined