Assessment of the Therapeutic Efficacy of Oncostatin M-preconditioned MSCs in the Bleomycin-induced Pulmonary Fibrosis Mouse Model

• Main Authors: Si Min Theng, 鄧思敏
• Other Authors: K. Y. Chong
• Format: Others
• Published: 2012
• Online Access: http://ndltd.ncl.edu.tw/handle/40288781243802172489

碩士 === 長庚大學 === 醫學生物技術暨檢驗學系 === 100 === Idiopathic pulmonary fibrosis (IPF) is characterized by an intricate cytokine network and abnormal deposition of mesenchymal cells. Recent studies indicated that Oncostatin M (OSM), a member of IL-6 family cytokine, was up-regulated in the bronchoalveolar lavage fluid (BALF) of patients with interstitial lung disease. Furthermore, exogenous administration of OSM into the lungs of mice resulted in a significant recruitment of inflammatory cells, as well as a dose-dependent increase of collagen deposition in the lungs. These results suggested that OSM is a potent mediator of lung inflammation and lung fibrosis. To date, there are no effective treatments for IPF. Recent studies indicated that mesenchymal stem cells (MSCs) significantly reduced damage in the alveoli and were engrafted at injury sites. Interestingly, OSM induced proliferation, differentiation of MSCs, and also induced Oncostatin M receptor (OSMR) expression in the cells. Moreover, OSM also activated HGF expression in fibroblast and might participate in repair after lung injury. Taken together, to improve the protective effect of the transplanted MSCs, we proposed to enrich OSMR overexpressed cell population of MSCs by OSM pretreatment, upon transplantation, OSM binding to the OSM receptor lead to activate signaling pathway from MSC and further induced cytoprotective genes for pulmonary fibrosis treatment. Our data showed that OSM-pretreatment induced OSMR, gp130 and HGF mRNA and protein expression in MSCs. When cocultured with OSM-pretreated MSCs and TGF-β1 treated MRC-5s, the fibrotic marker, the fibronectin mRNA expression was significantly down-regulated. Furthermore, intratracheal instillation of OSM-pretreated MSCs into BPF mouse model at day 3, eighteen days after treatment, the pulmonary respiratory function have shown significant improvement, the mRNA expression of inflammatory factors IL-1β, IL-6 and fibrotic factor collagen III, MMP-9 were significantly decreased in the lung tissues when compared to MSCs group. Our data indicated that anti-inflammation and anti-fibrotic ability were better than MSCs. In conclusion, we demonstrated that OSM-pretreated MSCs significant improves the therapeutic effect of the pulmonary fibrosis.