title: Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells.
abstract: BACKGROUND
  Mesenchymal stem cells (MSC) have not only been implicated in the development of lung diseases, but they have also been proposed as a future cell-based therapy for lung diseases. However, the cellular identity of the primary MSC in human lung tissues has not yet been reported. This study therefore aimed to identify and characterise the 'bona fide' MSC in human lungs and to investigate if the MSC numbers correlate with the development of bronchiolitis obliterans syndrome in lung-transplanted patients.
  
  
  METHODS
  Primary lung MSC were directly isolated or culture-derived from central and peripheral transbronchial biopsies of lung-transplanted patients and evaluated using a comprehensive panel of in vitro and in vivo assays.
  
  
  RESULTS
  Primary MSC were enriched in the CD90/CD105 mononuclear cell fraction with mesenchymal progenitor frequencies of up to four colony-forming units, fibroblast/100 cells. In situ staining of lung tissues revealed that CD90/CD105 MSCs were located perivascularly. MSC were tissue-resident and exclusively donor lung-derived even in biopsies obtained from patients as long as 16 years after transplantation. Culture-derived mesenchymal stromal cells showed typical in vitro MSC properties; however, xenotransplantation into non-obese diabetic/severe combined immunodeficient (NOD/SCID) mice showed that lung MSC readily differentiated into adipocytes and stromal tissues, but lacked significant in vivo bone formation.
  
  
  CONCLUSIONS
  These data clearly demonstrate that primary MSC in human lung tissues are not only tissue resident but also tissue-specific. The identification and phenotypic characterisation of primary lung MSC is an important first step in identifying the role of MSC in normal lung physiology and pulmonary diseases.
authors.affiliation: Department of Experimental Medical Science, Lung Biology Unit , Lund University , Lund , Sweden.
authors.forename: Sara
authors.initials: S
authors.lastname: Rolandsson
authors.affiliation: Department of Experimental Medical Science, Lung Biology Unit , Lund University , Lund , Sweden.
authors.forename: Annika
authors.initials: A
authors.lastname: Andersson Sjöland
authors.affiliation: Lund Stem Cell Center, Lund University , Lund , Sweden.
authors.forename: Jan C
authors.initials: JC
authors.lastname: Brune
authors.affiliation: Lund Stem Cell Center, Lund University , Lund , Sweden.
authors.forename: Hongzhe
authors.initials: H
authors.lastname: Li
authors.affiliation: Department of Endocrinology, Molecular Endocrinology Laboratory (KMEB) , University of Southern Denmark , Odense , Denmark.
authors.forename: Moustapha
authors.initials: M
authors.lastname: Kassem
authors.affiliation: Department of Clinical Genetics , University and Regional Laboratories, Lund University , Lund , Sweden.
authors.forename: Fredrik
authors.initials: F
authors.lastname: Mertens
authors.affiliation: School of Health and Society, Kristianstad University , Lund , Sweden.
authors.forename: Albert
authors.initials: A
authors.lastname: Westergren
authors.affiliation: Department of Respiratory Medicine and Allergology , Lund University and Skåne University Hospital , Lund , Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Eriksson
authors.affiliation: Department of Respiratory Medicine and Allergology , Lund University and Skåne University Hospital , Lund , Sweden.
authors.forename: Lennart
authors.initials: L
authors.lastname: Hansson
authors.affiliation: Department of Respiratory Medicine and Allergology , Lund University and Skåne University Hospital , Lund , Sweden.
authors.forename: Ingrid
authors.initials: I
authors.lastname: Skog
authors.affiliation: Department of Respiratory Medicine and Allergology , Lund University and Skåne University Hospital , Lund , Sweden.
authors.forename: Leif
authors.initials: L
authors.lastname: Bjermer
authors.affiliation: Lund Stem Cell Center, Lund University , Lund , Sweden ; Department of Hematology , Skåne University Hospital , Lund , Sweden.
authors.forename: Stefan
authors.initials: S
authors.lastname: Scheding
authors.affiliation: Department of Experimental Medical Science, Lung Biology Unit , Lund University , Lund , Sweden.
authors.forename: Gunilla
authors.initials: G
authors.lastname: Westergren-Thorsson
keywords: Lung Transplantation