TY - JOUR T1 - Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells JF - BMJ Open Respiratory Research JO - BMJ Open Resp Res DO - 10.1136/bmjresp-2014-000027 VL - 1 IS - 1 SP - e000027 AU - Sara Rolandsson AU - Annika Andersson Sjöland AU - Jan C Brune AU - Hongzhe Li AU - Moustapha Kassem AU - Fredrik Mertens AU - Albert Westergren AU - Leif Eriksson AU - Lennart Hansson AU - Ingrid Skog AU - Leif Bjermer AU - Stefan Scheding AU - Gunilla Westergren-Thorsson Y1 - 2014/05/01 UR - http://bmjopenrespres.bmj.com/content/1/1/e000027.abstract N2 - 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. ER -