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

Respiratory Research

Nelli Baal¹  Cornelia Brendel²  Gregor Bein¹  Achim D. Gruber⁴  Kristina Dietert⁴  Matthias Hecker³  Sabine Kranz¹  Inna Schevtschenko¹  Philipp Krug¹  Anne Lippitsch¹  Holger Hackstein¹ 

[1] Institute for Clinical Immunology and Transfusion Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), University Hospital Giessen und Marburg, Justus-Liebig-University Giessen, Langhansstr. 7, Giessen, D-35390, Germany;Department of Hematology, Oncology and Immunology, Philipps University Marburg, University Hospital Giessen und Marburg, Marburg, Germany;Department of Internal Medicine II, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), University Hospital Giessen und Marburg, Justus-Liebig-University Giessen, Giessen, Germany;Department of Veterinary Pathology, Freie Universität Berlin, Robert-von-Ostertag-Str. 15, Berlin, Germany

关键词: Acute lung injury;    Klebsiella pneumonia;    Mesenchymal stem cells;    Pneumonia;   

Others  :  1233504
DOI  :  10.1186/s12931-015-0288-1

 received in 2014-11-12, accepted in 2015-10-02,  发布年份 2015

【 摘 要 】

Background

Numerous studies have described the immunosuppressive capacity of mesenchymal stem cells (MSC) but these studies use mixtures of heterogeneous progenitor cells for in vitro expansion. Recently, multipotent MSC have been prospectively identified in murine bone marrow (BM) on the basis of PDFGRa ⁺SCA1 ⁺CD45 ⁻TER119 ⁻(PαS) expression but the immunomodulatory capacity of these MSC is unknown.

Methods

We isolated PαS MSC by high-purity FACS sorting of murine BM and after in vitro expansion we analyzed the in vivo immunomodulatory activity during acute pneumonia. PαS MSC (1 × 10 ⁶ ) were applied intratracheally 4 h after acute respiratory Klebsiella pneumoniae induced infection.

Results

PαS MSC treatment resulted in significantly reduced alveolitis and protein leakage in comparison to mock-treated controls. PαS MSC-treated mice exhibited significantly reduced alveolar TNF-α and IL-12p70 expression, while IL-10 expression was unaffected. Dissection of respiratory dendritic cell (DC) subsets by multiparameter flow cytometry revealed significantly reduced lung DC infiltration and significantly reduced CD86 costimulatory expression on lung CD103 ⁺DC in PαS MSC-treated mice. In the post-acute phase of pneumonia, PαS MSC-treated animals exhibited significantly reduced respiratory IL-17 ⁺CD4 ⁺T cells and IFN-γ ⁺CD4 ⁺T cells. Moreover, PαS MSC treatment significantly improved overall pneumonia survival and did not increase bacterial load.

Conclusion

In this study we demonstrated for the first time the feasibility and in vivo immunomodulatory capacity of prospectively defined MSC in pneumonia.

【 授权许可】

   
2015 Hackstein et al.

【 图 表 】

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