Oncostatin M-preconditioned mesenchymal stem cells alleviate bleomycin-induced pulmonary fibrosis through paracrine effects of the hepatocyte growth factor

Ying Wei Lan, Si Min Theng, Tsung Teng Huang, Kong Bung Choo, Chuan Mu Chen, Han Pin Kuo, Kowit Yu Chong

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20 Citations (Scopus)


Mesenchymal stem cells (MSCs) are widely considered for treatment of pulmonary fibrosis based on the anti-inflammatory, antifibrotic, antiapoptotic, and regenerative properties of the cells. Recently, elevated levels of oncostatin M (OSM) have been reported in the bronchoalveolar lavage fluid of a pulmonary fibrosis animal model and in patients. In this work, we aimed to prolong engrafted MSC survival and to enhance the effectiveness of pulmonary fibrosis transplantation therapy by using OSM-preconditioned MSCs. OSM-preconditioned MSCs were shown to overexpress type 2 OSM receptor (gp130/OSMRβ) and exhibited high susceptibility to OSM, resulting in upregulation of the paracrine factor, hepatocyte growth factor (HGF). Moreover, OSM-preconditioned MSCs enhanced cell proliferation and migration, attenuated transforming growth factor-β1- or OSM-induced extracellular matrix production in MRC-5 fibroblasts through paracrine effects. In bleomycin-induced lung fibrotic mice, transplantation of OSM-preconditioned MSCs significantly improved pulmonary respiratory functions and downregulated expression of inflammatory factors and fibrotic factors in the lung tissues. Histopathologic examination indicated remarkable amelioration of the lung fibrosis. LacZ-tagged MSCs were detected in the lung tissues of the OSM-preconditioned MSC-treated mice 18 days after post-transplantation. Taken together, our data further demonstrated that HGF upregulation played an important role in mediating the therapeutic effects of transplanted OSMpreconditioned MSCs in alleviating lung fibrosis in the mice.

Original languageEnglish
Pages (from-to)1006-1017
Number of pages12
JournalStem cells translational medicine
Issue number3
Publication statusPublished - Mar 1 2017
Externally publishedYes



  • Bleomycin-induced pulmonary fibrosis
  • Hepatocyte growth factor
  • Oncostatin M
  • Preconditioning
  • Stem cells

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

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