Background

Marrow mesenchymal stem cells (MSCs), especially bone MSCs (BMSCs), play a vital role in immunomodulation of graft rejection but many shortcomings limit its application. In this study, we aimed to investigate the modulation effect of MSCs from gingiva (GMSCs) on the rejection of rat liver transplantation model and to explore the potential mechanisms.

Methods

GMSCs were obtained from human gingival tissues and BMSCs were harvested from Brown Norway (BN) rats. The siRNA that mediated knockdown of Fas ligand (FASL) expression in GMSCs (FASL-/-GMSCs) was transfected using lentivirus plasmid. Rat orthotopic liver transplantation model was established. The rats were divided randomly into four groups: normal saline (NS) group, FASL-/-GMSCs group, BMSCs group, and GMSCs group, all of which were injected the solution via dorsal vein of penis to construct the rat rejection model Graft survival and liver function indexes were measured. The immunological reactions of recipients including immune-cytokines, T-helper type 17 (Th17) and regulatory T cells (Treg) were also evaluated by flow cytometry.

Results

The graft survival of recipient rats in the GMSCs group was significantly prolonged in comparison with that of the NS, FASL-/-GMSCs and BMSCs group. GMSCs remarkably decreased the levels of AST, ALT and TBIL. As for immune-cytokines, serum levels of IL-2, IFN-γ and Th 17 in recipient rats from the GMSCs group reduced significantly compared with that of other three groups, while increased serum IL-10 and TGF-β expressions as well as peripheral serum Treg were also observed in GMSCs group.

Conclusion

GMSCs exert immunoprotection on liver transplants by regulating FAS-FASL pathway. The current study firstly provides basis for GMSCs to be used in clinical anti-rejection after liver transplantation.

中文翻译：

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人牙龈源性基质细胞通过调节FAS / FASL途径对大鼠肝移植模型产生免疫保护作用

背景

骨髓间充质干细胞（MSC），尤其是骨MSC（BMSC），在免疫排斥反应中起着至关重要的作用，但许多缺点限制了其应用。在这项研究中，我们旨在研究牙龈间充质干细胞（GMSCs）对大鼠肝移植模型排斥反应的调节作用，并探讨其潜在机制。

方法

GMSC获自人牙龈组织，BMSC获自Brown Norway（BN）大鼠。使用慢病毒质粒转染介导在GMSC（FASL-/-GMSC）中Fas配体（FASL）表达的敲低的siRNA。建立大鼠原位肝移植模型。将大鼠随机分为四组：生理盐水（NS）组，FASL-/-GMSCs组，BMSCs组和GMSCs组，均通过阴茎背静脉注射溶液以建立大鼠排斥反应模型测定肝功能指标。还通过流式细胞术评估了包括免疫细胞因子，17型T辅助细胞（Th17）和调节性T细胞（Treg）在内的受体的免疫反应。

结果

与NS，FASL-/-GMSCs和BMSCs组相比，GMSCs组的受体大鼠的移植物存活期显着延长。GMSC显着降低AST，ALT和TBIL的水平。至于免疫细胞因子，与其他三组相比，GMSCs组的大鼠的血清IL-2，IFN-γ和Th 17的水平明显降低，而血清IL-10和TGF-β的表达增加，并且GMSCs组也观察到外周血Treg。

结论

GMSC通过调节FAS-FASL途径对肝脏移植物发挥免疫保护作用。本研究首先为GMSCs在肝移植后临床抗排斥反应中的应用提供了依据。