254. Hepatocyte Growth Factor Gene Modification Enhances the Inflammation-Alleviating Effect of Umbilical Cord Derived Mesenchymal Stem Cells in a Bronchiolitis Obliterans Model

BACKGROUNDS: Bronchiolitis obliterans is a serious, steadily, noninfectious, and fatal pulmonary complication. Currently specific and effective therapeutics for prevention or reversal of bronchiolitis obliterans is lacking. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF) gene modified mesenchymal stem cells (MSCs) on bronchiolitis obliterans.METHODS: A mouse model of experimental bronchiolitis obliterans was established by subcutaneously transplanting the tracheas from C57BL/6 mice into Balb/C recipients. These model mice were administered saline, Ad-HGF-modified human umbilical cord-MSCs (MSCs-HGF) or Ad-Null-modified MSCs (MSCs-Null). The distribution of the transplanted cells was detected by using real-time PCR (rt-PCR). The therapeutic effects of MSCs-Null and MSCs-HGF were evaluated by using FACS for lymphocyte immunophenotype of spleen, ELISA and rt-PCR for cytokine expression, and histopathological analysis for the transplanted trachea.RESULTS: The administrated MSCs mainly distributed in the transplanted trachea, blood, liver and lung of the recipients; HGF gene modification could enhance the engraftment of MSCs. The histopathological recovery of allografts tracheas was improved significantly after MSCs-Null and MSCs-HGF treatment and the beneficial effects were particularly observed in MSCs-HGFtreated mice. Furthermore, the allo-transplantation induced immunophenotype disorders of the spleen cells, including Treg, Th1, Th2 and Th17 cells, were attenuated in both cell treated groups. MSCs-HGF treatment reduced expression and secretion of inflammation cytokines interferon-gamma and increased expression of anti-inflammatory cytokine IL-4 and IL-10. It also decreased the expression level of the profibrosis factor transforming growth factor-beta.b.CONCLUSIONS: Treatment of bronchiolitis obliterans with HGF gene modified MSCs results in reduction of local inflammation and promotion in recovery of allografts tracheas histopathology in a mouse model. These findings might provide an effective therapeutic strategy for bronchiolitis obliterans.