The Pathology of Bleomycin-Induced Fibrosis Is Associated with Loss of Resident Lung Mesenchymal Stem Cells That Regulate Effector T-cell Proliferation

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  • Du Jun
    Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, Colorado, USA
  • Chrystelle Garat
    Department of Medicine,University of Colorado Denver, Aurora, Colorado, USA
  • James West
    Division of Allergy, Pulmonary, and Critical Care Medicine, Department of Medicine,Vanderbilt University Medical School, Nashville, Tennessee, USA
  • Nathalie Thorn
    Division of Pulmonary, Allergy and Critical Care Medicine, Simmons Center for Interstitial Lung Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  • Kelsey Chow
    Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, Colorado, USA
  • Timothy Cleaver
    Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, Colorado, USA
  • Timothy Sullivan
    Department of Medicine,University of Colorado Denver, Aurora, Colorado, USA
  • Enrique C. Torchia
    Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, Colorado, USA
  • Christine Childs
    Cancer Center,University of Colorado Denver, Aurora, Colorado, USA
  • Theodore Shade
    Cancer Center,University of Colorado Denver, Aurora, Colorado, USA
  • Mehrdad Tadjali
    Department of Hematology, St. Jude Children's Hospital, Memphis, Tennessee, USA
  • Abigail Lara
    Department of Medicine,University of Colorado Denver, Aurora, Colorado, USA
  • Eva Nozik-Grayck
    Critical Care Medicine, Department of Pediatrics, University of Colorado Denver, Aurora, Colorado, USA
  • Stephen Malkoski
    Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, Colorado, USA
  • Brian Sorrentino
    Department of Hematology, St. Jude Children's Hospital, Memphis, Tennessee, USA
  • Barbara Meyrick
    Department of Pathology, Vanderbilt University Medical School, Nashville, Tennessee, USA
  • Dwight Klemm
    Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, Colorado, USA
  • Mauricio Rojas
    Division of Pulmonary, Allergy and Critical Care Medicine, Simmons Center for Interstitial Lung Diseases, Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, USA
  • David H. Wagner
    Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, Colorado, USA
  • Susan M. Majka
    Charles C. Gates Center for Regenerative Medicine and Stem Cell Biology Program, University of Colorado Denver, Aurora, Colorado, USA

書誌事項

公開日
2011-04-01
権利情報
  • https://academic.oup.com/journals/pages/open_access/funder_policies/chorus/standard_publication_model
DOI
  • 10.1002/stem.604
公開者
Oxford University Press (OUP)

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説明

<jats:title>Abstract</jats:title> <jats:p>Tissue-resident mesenchymal stem cells (MSCs) are important regulators of tissue repair or regeneration, fibrosis, inflammation, angiogenesis, and tumor formation. Here, we define a population of resident lung MSCs (luMSCs) that function to regulate the severity of bleomycin injury via modulation of the T-cell response. Bleomycin-induced loss of these endogenous luMSCs and elicited fibrosis (pulmonary fibrosis), inflammation, and pulmonary arterial hypertension (PAH). Replacement of resident stem cells by administration of isolated luMSCs attenuated the bleomycin-associated pathology and mitigated the development of PAH. In addition, luMSC modulated a decrease in numbers of lymphocytes and granulocytes in bronchoalveolar fluid and demonstrated an inhibition of effector T-cell proliferation in vitro. Global gene expression analysis indicated that the luMSCs are a unique stromal population differing from lung fibroblasts in terms of proinflammatory mediators and profibrotic pathways. Our results demonstrate that luMSCs function to protect lung integrity after injury; however, when endogenous MSCs are lost, this function is compromised illustrating the importance of this novel population during lung injury. The definition of this population in vivo in both murine and human pulmonary tissue facilitates the development of a therapeutic strategy directed at the rescue of endogenous cells to facilitate lung repair during injury.</jats:p>

収録刊行物

  • Stem Cells

    Stem Cells 29 (4), 725-735, 2011-04-01

    Oxford University Press (OUP)

被引用文献 (3)*注記

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