Open AccessHuman Adipose‐Derived Stem Cells Ameliorate Cigarette Smoke‐Induced Murine Myelosuppression via Secretion of TSG‐6
Author(s) -
Xie Jie,
Broxmeyer Hal E.,
Feng Dongni,
Schweitzer Kelly S.,
Yi Ru,
Cook Todd G.,
Chitteti Brahmananda R.,
Barwinska Daria,
Traktuev Dmitry O.,
Van Demark Mary J.,
Justice Matthew J.,
Ou Xuan,
Srour Edward F.,
Prockop Darwin J.,
Petrache Irina,
March Keith L.
Publication year - 2015
Publication title -
stem cells
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.159
H-Index - 229
eISSN - 1549-4918
pISSN - 1066-5099
DOI - 10.1002/stem.1851
Subject(s) - stem cell , bone marrow , clonogenic assay , biology , haematopoiesis , progenitor cell , adipose tissue , bone marrow stem cell , pharmacology , microbiology and biotechnology , cancer research , immunology , in vivo , endocrinology
Objective: Bone marrow‐derived hematopoietic stem and progenitor cells (HSC/HPC) are critical to homeostasis and tissue repair. The aims of this study were to delineate the myelotoxicity of cigarette smoking (CS) in a murine model, to explore human adipose‐derived stem cells (hASC) as a novel approach to mitigate this toxicity, and to identify key mediating factors for ASC activities. Methods: C57BL/6 mice were exposed to CS with or without i.v. injection of regular or siRNA‐transfected hASC. For in vitro experiments, cigarette smoke extract was used to mimic the toxicity of CS exposure. Analysis of bone marrow HPC was performed both by flow cytometry and colony‐forming unit assays. Results: In this study, we demonstrate that as few as 3 days of CS exposure results in marked cycling arrest and diminished clonogenic capacity of HPC, followed by depletion of phenotypically defined HSC/HPC. Intravenous injection of hASC substantially ameliorated both acute and chronic CS‐induced myelosuppression. This effect was specifically dependent on the anti‐inflammatory factor TSG‐6, which is induced from xenografted hASC, primarily located in the lung and capable of responding to host inflammatory signals. Gene expression analysis within bone marrow HSC/HPC revealed several specific signaling molecules altered by CS and normalized by hASC. Conclusion: Our results suggest that systemic administration of hASC or TSG‐6 may be novel approaches to reverse CS‐induced myelosuppression. S tem C ells 2015;33:468–478