title: Attenuation of early airway obstruction by mesenchymal stem cells in a murine model of heterotopic tracheal transplantation.
abstract: BACKGROUND
  Long-term success in lung transplantation is limited by obliterative bronchiolitis (OB). Presently, complete understanding of the mechanisms of OB has been elusive. Bone marrow-derived mesenchymal stem cells (MSC) have been shown to modulate repair of the injured lung in multiple disease models. We hypothesized that the injection of MSC would prevent development of early airway obstruction (AO) in the heterotopic tracheal transplant model.
  
  
  METHODS
  Forty-four tracheas from BALB/c and C57BL/6 donors were transplanted into 22 C57BL/6 recipients. At the time of transplant, 13 of the allogeneic recipient mice were injected with 5 × 10(5) MSC from various murine sources. To confirm the role of the immune response in the generation of AO we used a permeable inhibitor of nuclear factor-kappaB (NF-κB) in 11 recipients after transplantation with 22 BALB/c tracheas.
  
  
  RESULTS
  After transplantation, administration of MSC inhibited intraluminal obstruction by collagen in 98% of the mice and transforming factor-beta (TGF-β) expression decreased to levels similar to those observed in isograft controls. These effects were associated with a significant (p < 0.05) increase in expression of the anti-inflammatory cytokine interleukin-10 (IL-10). NF-κB inhibitor showed decreased expression of transforming growth factor-beta (TGF-β) in the Day 7 and Day 14 groups, resulting in a 60% reduction of luminal obstruction as well as a decrease in inflammatory cells to the airway.
  
  
  CONCLUSIONS
  Our observations suggest that administration of MSC prevents development of airway occlusion in a mouse model, probably through the modulated immune response altering TGF-β expression.
authors.affiliation: Division of Pulmonary, Allergy and Critical Care Medicine, Department of Medicine, Emory University School of Medicine, Atlanta, Georgia, USA.
authors.forename: Daniel A
authors.initials: DA
authors.lastname: Grove
authors.forename: Jianguo
authors.initials: J
authors.lastname: Xu
authors.forename: Robert
authors.initials: R
authors.lastname: Joodi
authors.forename: Edilson
authors.initials: E
authors.lastname: Torres-Gonzales
authors.forename: David
authors.initials: D
authors.lastname: Neujahr
authors.forename: Ana L
authors.initials: AL
authors.lastname: Mora
authors.forename: Mauricio
authors.initials: M
authors.lastname: Rojas
mesh_terms: D000402:Airway Obstruction / Q000517:prevention & control*; D000818:Animals; D004195:Disease Models, Animal; D005260:Female; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D014132:Trachea / Q000637:transplantation*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016042:Transplantation, Heterotopic; D014184:Transplantation, Homologous
chemical_list: D016212:Transforming Growth Factor beta