title: Pretreatment with bone marrow-derived mesenchymal stromal cell-conditioned media confers pulmonary ischemic tolerance.
abstract: OBJECTIVE
  Mesenchymal stromal cell-based therapies have demonstrated efficacy in treating a variety of diseases. Despite the potential benefits, there are still significant hurdles that need to be overcome for clinical use. We describe a cell-free-based immunotherapy approach for inducing pulmonary ischemic tolerance by using mesenchymal stromal cell-conditioned media.
  
  
  METHODS
  In our well-established lung ischemia-reperfusion model, we pretreated with mesenchymal stromal cell-conditioned media 30 minutes before injury. To determine the degree of lung injury, we assessed for changes in lung vascular permeability, proinflammatory cytokines and cellular infiltrates in bronchoalveolar lavage, and histopathology. Macrophage and T-cell subsets were assessed by immunohistochemistry.
  
  
  RESULTS
  Pretreatment with mesenchymal stromal cell-conditioned media conferred protection against lung ischemia-reperfusion injury. This protection is characterized by a significant reduction in proinflammatory cytokines, a decrease in infiltrating inflammatory cells, and increases in M2-like macrophages and regulatory T cells.
  
  
  CONCLUSIONS
  Cell-free mesenchymal stromal cell-conditioned media therapy confers pulmonary ischemic tolerance. This therapy uses paracrine factors that provide beneficial protective effects by immunomodulating the inflammatory response in resident and infiltrating cell subsets.
authors.affiliation: Department of Surgery, University of Washington School of Medicine, Seattle, Wash; Center for Lung Biology, University of Washington, Seattle, Wash. Electronic address: bhwang@uw.edu.
authors.forename: Billanna
authors.initials: B
authors.lastname: Hwang
authors.affiliation: Center for Lung Biology, University of Washington, Seattle, Wash; Department of Medicine, University of Washington School of Medicine, Seattle, Wash.
authors.forename: W Conrad
authors.initials: WC
authors.lastname: Liles
authors.affiliation: Center for Lung Biology, University of Washington, Seattle, Wash.
authors.forename: Rachel
authors.initials: R
authors.lastname: Waworuntu
authors.affiliation: Department of Surgery, University of Washington School of Medicine, Seattle, Wash; Center for Lung Biology, University of Washington, Seattle, Wash.
authors.forename: Michael S
authors.initials: MS
authors.lastname: Mulligan
mesh_terms: D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002199:Capillary Permeability; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000378:metabolism*; D016207:Cytokines / Q000378:metabolism; D004195:Disease Models, Animal; D007167:Immunotherapy / Q000379:methods*; D018836:Inflammation Mediators / Q000378:metabolism; D008168:Lung / Q000098:blood supply / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D055370:Lung Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D008264:Macrophages / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000276:immunology / Q000378:metabolism*; D019899:Paracrine Communication; D020318:Rats, Long-Evans; D015427:Reperfusion Injury / Q000276:immunology / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D016176:T-Lymphocyte Subsets / Q000378:metabolism; D013997:Time Factors
chemical_list: D017077:Culture Media, Conditioned; D016207:Cytokines; D018836:Inflammation Mediators
keywords: acute lung graft rejection; lung ischemia–reperfusion injury; mesenchymal stromal (stem) cell therapy; mesenchymal stromal (stem)–conditioned media