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Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells
  1. Sara Rolandsson1,
  2. Annika Andersson Sjöland1,
  3. Jan C Brune2,
  4. Hongzhe Li2,
  5. Moustapha Kassem3,
  6. Fredrik Mertens4,
  7. Albert Westergren5,
  8. Leif Eriksson6,
  9. Lennart Hansson6,
  10. Ingrid Skog6,
  11. Leif Bjermer6,
  12. Stefan Scheding2,7 and
  13. Gunilla Westergren-Thorsson1
  1. 1Department of Experimental Medical Science, Lung Biology Unit, Lund University, Lund, Sweden
  2. 2Lund Stem Cell Center, Lund University, Lund, Sweden
  3. 3Department of Endocrinology, Molecular Endocrinology Laboratory (KMEB), University of Southern Denmark, Odense, Denmark
  4. 4Department of Clinical Genetics, University and Regional Laboratories, Lund University, Lund, Sweden
  5. 5School of Health and Society, Kristianstad University, Lund, Sweden
  6. 6Department of Respiratory Medicine and Allergology, Lund University and Skåne University Hospital, Lund, Sweden
  7. 7Department of Hematology, Skåne University Hospital, Lund, Sweden
  1. Correspondence to Dr Sara Rolandsson; Sara.Rolandsson{at}med.lu.se

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.

  • Lung Transplantation

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