title: Human adipose-derived stem cells ameliorate cigarette smoke-induced murine myelosuppression via secretion of TSG-6.
abstract: 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.
  
  
  CONCLUSIONS
  Our results suggest that systemic administration of hASC or TSG-6 may be novel approaches to reverse CS-induced myelosuppression.
authors.affiliation: Department of Cellular & Integrative Physiology, Herman B Wells Center for Pediatric Research, Indiana University, Indianapolis, Indiana, USA; Indiana Center for Vascular Biology and Medicine, VC-CAST Signature Center, Department of Medicine, Herman B Wells Center for Pediatric Research, Indiana University, Indianapolis, Indiana, USA; VA Center for Regenerative Medicine Indianapolis, "Richard L. Roudebush" VA Medical Center, Indianapolis, Indiana, USA.
authors.forename: Jie
authors.initials: J
authors.lastname: Xie
authors.forename: Hal E
authors.initials: HE
authors.lastname: Broxmeyer
authors.forename: Dongni
authors.initials: D
authors.lastname: Feng
authors.forename: Kelly S
authors.initials: KS
authors.lastname: Schweitzer
authors.forename: Ru
authors.initials: R
authors.lastname: Yi
authors.forename: Todd G
authors.initials: TG
authors.lastname: Cook
authors.forename: Brahmananda R
authors.initials: BR
authors.lastname: Chitteti
authors.forename: Daria
authors.initials: D
authors.lastname: Barwinska
authors.forename: Dmitry O
authors.initials: DO
authors.lastname: Traktuev
authors.forename: Mary J
authors.initials: MJ
authors.lastname: Van Demark
authors.forename: Matthew J
authors.initials: MJ
authors.lastname: Justice
authors.forename: Xuan
authors.initials: X
authors.lastname: Ou
authors.forename: Edward F
authors.initials: EF
authors.lastname: Srour
authors.forename: Darwin J
authors.initials: DJ
authors.lastname: Prockop
authors.forename: Irina
authors.initials: I
authors.lastname: Petrache
authors.forename: Keith L
authors.initials: KL
authors.lastname: March
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D015815:Cell Adhesion Molecules / Q000378:metabolism* / Q000494:pharmacology; D004195:Disease Models, Animal; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D016688:Mice, Inbred NOD; D016513:Mice, SCID; D038042:Myelopoiesis; D012907:Smoking / Q000009:adverse effects* / Q000473:pathology; D033581:Stem Cell Transplantation; D013234:Stem Cells / Q000378:metabolism* / Q000473:pathology
chemical_list: D015815:Cell Adhesion Molecules; C072273:TNFAIP6 protein, human
keywords: Adipose stem cells; Hematopoietic progenitors; Toxicity; Xenogeneic stem cell transplantation