title: Endothelin-1 governs proliferation and migration of bronchoalveolar lavage-derived lung mesenchymal stem cells in bronchiolitis obliterans syndrome.
abstract: BACKGROUND
  Bronchiolitis obliterans syndrome (BOS) has an incidence of 57% at 5 years after lung transplantation, accounts for 30% of all deaths 3 years posttransplant and because treatment options are extremely limited, it constitutes a significant health care problem. Adult mesenchymal stem cells (MSCs) play a role in lung turnover; however, their role in BOS remains unknown.
  
  
  METHODS
  MSCs were isolated from bronchoalveolar lavage (BAL) in 101 lung allograft recipients. BAL was screened by protein array and MSCs were analyzed by real-time polymerase chain reaction, proliferation, migration, and enzyme linked immunosorbent assays.
  
  
  RESULTS
  Multipotent MSCs were isolated from BAL of lung recipients independent of BOS presence. However, MSCs from BOS patients proliferated at higher rates (P<0.001) and were associated with higher α-smooth muscle actin (P = 0.03) but lower surfactant protein B (P = 0.02) compared with those from no-BOS patients. Histological analysis revealed that MSCs are abundant in lung tissue of BOS patients. MSCs from BOS patients produced higher endothelin-1 (ET-1) amounts (P<0.001) compared with those from no-BOS; and ET-1 stimulated whereas ET-1 blockade suppressed MSC proliferation, migration, and differentiation.
  
  
  CONCLUSIONS
  These results indicate that MSCs are associated with BOS and are governed by ET-1. Targeting MSCs by ET-1 blockade might be useful in BOS treatment.
authors.affiliation: Department of Cardiothoracic Surgery, Medical University of Vienna, Vienna, Austria.
authors.forename: Mohamed
authors.initials: M
authors.lastname: Salama
authors.forename: Olena
authors.initials: O
authors.lastname: Andrukhova
authors.forename: Peter
authors.initials: P
authors.lastname: Jaksch
authors.forename: Shahrokh
authors.initials: S
authors.lastname: Taghavi
authors.forename: Walter
authors.initials: W
authors.lastname: Kelpetko
authors.forename: Gerhard
authors.initials: G
authors.lastname: Dekan
authors.forename: Seyedhossein
authors.initials: S
authors.lastname: Aharinejad
mesh_terms: D000199:Actins / Q000378:metabolism; D000328:Adult; D000368:Aged; D001989:Bronchiolitis Obliterans / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D018893:Bronchoalveolar Lavage; D002454:Cell Differentiation / Q000502:physiology; D002465:Cell Movement / Q000502:physiology*; D049109:Cell Proliferation; D015331:Cohort Studies; D019332:Endothelin-1 / Q000502:physiology*; D005260:Female; D006801:Humans; D008168:Lung / Q000378:metabolism / Q000473:pathology*; D016040:Lung Transplantation / Q000473:pathology / Q000502:physiology; D008297:Male; D059630:Mesenchymal Stem Cells / Q000473:pathology / Q000502:physiology*; D008875:Middle Aged; D011498:Protein Precursors / Q000378:metabolism; D011510:Proteolipids / Q000378:metabolism
chemical_list: C541116:ACTA2 protein, human; D000199:Actins; D019332:Endothelin-1; D011498:Protein Precursors; D011510:Proteolipids; C105511:surfactant protein B propeptide