Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

Sara Rolandsson, Annika Andersson Sjöland, Jan C Brune, Hongzhe Li, Moustapha Kassem, Fredrik Mertens, Albert Westergren, Leif Eriksson, Lennart Hansson, Ingrid Skog, Leif Bjermer, Stefan Scheding, Gunilla Westergren-Thorsson

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

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.

OriginalsprogEngelsk
TidsskriftB M J Open Respiratory Research
Vol/bind1
Udgave nummer1
Sider (fra-til)e000027
DOI
StatusUdgivet - 2014

Fingeraftryk

Mesenchymal Stromal Cells
Lung
Lung Diseases
SCID Mice
Adipocytes
Osteogenesis
Fibroblasts

Citer dette

Rolandsson, Sara ; Andersson Sjöland, Annika ; Brune, Jan C ; Li, Hongzhe ; Kassem, Moustapha ; Mertens, Fredrik ; Westergren, Albert ; Eriksson, Leif ; Hansson, Lennart ; Skog, Ingrid ; Bjermer, Leif ; Scheding, Stefan ; Westergren-Thorsson, Gunilla. / Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells. I: B M J Open Respiratory Research. 2014 ; Bind 1, Nr. 1. s. e000027.
@article{57832b48627945e889067444e6f99ce3,
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.",
author = "Sara Rolandsson and {Andersson Sj{\"o}land}, Annika and Brune, {Jan C} and Hongzhe Li and Moustapha Kassem and Fredrik Mertens and Albert Westergren and Leif Eriksson and Lennart Hansson and Ingrid Skog and Leif Bjermer and Stefan Scheding and Gunilla Westergren-Thorsson",
year = "2014",
doi = "10.1136/bmjresp-2014-000027",
language = "English",
volume = "1",
pages = "e000027",
journal = "B M J Open Respiratory Research",
issn = "2052-4439",
publisher = "B M J Group",
number = "1",

}

Rolandsson, S, Andersson Sjöland, A, Brune, JC, Li, H, Kassem, M, Mertens, F, Westergren, A, Eriksson, L, Hansson, L, Skog, I, Bjermer, L, Scheding, S & Westergren-Thorsson, G 2014, 'Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells', B M J Open Respiratory Research, bind 1, nr. 1, s. e000027. https://doi.org/10.1136/bmjresp-2014-000027

Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells. / Rolandsson, Sara; Andersson Sjöland, Annika; Brune, Jan C; Li, Hongzhe; Kassem, Moustapha; Mertens, Fredrik; Westergren, Albert; Eriksson, Leif; Hansson, Lennart; Skog, Ingrid; Bjermer, Leif; Scheding, Stefan; Westergren-Thorsson, Gunilla.

I: B M J Open Respiratory Research, Bind 1, Nr. 1, 2014, s. e000027.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Primary mesenchymal stem cells in human transplanted lungs are CD90/CD105 perivascularly located tissue-resident cells

AU - Rolandsson, Sara

AU - Andersson Sjöland, Annika

AU - Brune, Jan C

AU - Li, Hongzhe

AU - Kassem, Moustapha

AU - Mertens, Fredrik

AU - Westergren, Albert

AU - Eriksson, Leif

AU - Hansson, Lennart

AU - Skog, Ingrid

AU - Bjermer, Leif

AU - Scheding, Stefan

AU - Westergren-Thorsson, Gunilla

PY - 2014

Y1 - 2014

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.

AB - 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.

U2 - 10.1136/bmjresp-2014-000027

DO - 10.1136/bmjresp-2014-000027

M3 - Journal article

VL - 1

SP - e000027

JO - B M J Open Respiratory Research

JF - B M J Open Respiratory Research

SN - 2052-4439

IS - 1

ER -