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

Research output: Contribution to journalArticle

17 Citations (Scopus)

Abstract

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
Volume6
Issue number3
DOIs
Publication statusPublished - Mar 1 2017
Externally publishedYes

Fingerprint

Oncostatin M
Hepatocyte Growth Factor
Pulmonary Fibrosis
Bleomycin
Mesenchymal Stromal Cells
Lung
Oncostatin M Type II Receptor
Fibrosis
Up-Regulation
Transplantation
Lung Transplantation
Bronchoalveolar Lavage Fluid
Transforming Growth Factors
Therapeutic Uses
Cell Movement
Extracellular Matrix
Cell Survival
Anti-Inflammatory Agents
Down-Regulation
Animal Models

Keywords

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

ASJC Scopus subject areas

  • Developmental Biology
  • Cell Biology

Cite this

Oncostatin M-preconditioned mesenchymal stem cells alleviate bleomycin-induced pulmonary fibrosis through paracrine effects of the hepatocyte growth factor. / Lan, Ying Wei; Theng, Si Min; Huang, Tsung Teng; Choo, Kong Bung; Chen, Chuan Mu; Kuo, Han Pin; Chong, Kowit Yu.

In: Stem cells translational medicine, Vol. 6, No. 3, 01.03.2017, p. 1006-1017.

Research output: Contribution to journalArticle

Lan, Ying Wei ; Theng, Si Min ; Huang, Tsung Teng ; Choo, Kong Bung ; Chen, Chuan Mu ; Kuo, Han Pin ; Chong, Kowit Yu. / Oncostatin M-preconditioned mesenchymal stem cells alleviate bleomycin-induced pulmonary fibrosis through paracrine effects of the hepatocyte growth factor. In: Stem cells translational medicine. 2017 ; Vol. 6, No. 3. pp. 1006-1017.
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