Hepatocyte growth factor enhances the inflammation-alleviating effect of umbilical cord-derived mesenchymal stromal cells in a bronchiolitis obliterans model

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• 作者：Xiao-Pei Cao¹ ; ² ; Dong-Mei Han³ ; Li Zhao⁴ ; Zi-Kuan Guo² ; Feng-Jun Xiao² ; Yi-Kun Zhang² ; Xiao-Yan Zhang² ; Li-Sheng Wang² ; Heng-Xiang Wang³ ; ^{wanghengxiang123@aliyun.com" class="auth_mail" title="E-mail the corresponding author} ; Hua Wang² ; ^{wanghua@bmi.ac.cn" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Bronchiolitis obliterans ; Hepatocyte growth factor ; Th cells ; Treg cells ; Umbilical cord&ndash ; derived mesenchymal stromal cells
• 刊名：Cytotherapy
• 出版年：2016
• 出版时间：March 2016
• 年：2016
• 卷：18
• 期：3
• 页码：402-412
• 全文大小：3136 K

文摘

Specific and effective therapy for prevention or reversal of bronchiolitis obliterans (BO) is lacking. In this study, we evaluated the therapeutic effect of hepatocyte growth factor (HGF) gene modified mesenchymal stromal cells (MSCs) on BO.

Methods

A mouse model of experimental BO was established by subcutaneously transplanting the tracheas from C57BL/6 mice into Balb/C recipients, which were then administered saline, Ad-HGF-modified human umbilical cord-MSCs (MSCs-HGF) or Ad-Null-modified MSCs (MSCs-Null). The therapeutic effects of MSCs-Null and MSCs-HGF were evaluated by using fluorescence-activated cell sorting (FACS) for lymphocyte immunophenotype of spleen, enzyme-linked immunosorbent assay (ELISA) and real-time polymerase chain reaction (rt-PCR) for cytokine expression, and histopathological analysis for the transplanted trachea.

Results

The histopathologic recovery of allograft tracheas was improved significantly after MSCs-Null and MSCs-HGF treatment and the beneficial effects were particularly observed in MSCs-HGF–treated mice. Furthermore, the allo-transplantation–induced immunophenotype disorders of the spleen, including regulatory T (Treg), T helper (Th)1, Th2 and Th17, were attenuated in both cell-treated groups. MSCs-HGF treatment reduced expression and secretion of inflammation cytokines interferon-gamma (IFN-γ), and increased expression of anti-inflammatory cytokine interleukin (IL)-4 and IL-10. It also decreased the expression level of the profibrosis factor transforming growth factor (TGF)-β.

Conclusion

Treatment of BO with HGF gene modified MSCs results in reduction of local inflammation and promotion in recovery of allograft trachea histopathology. These findings might provide an effective therapeutic strategy for BO.