骨髓源干细胞通过下调白细胞介素-17减轻肝纤维化。

Bone marrow-derived stem cells ameliorate hepatic fibrosis by down-regulating interleukin-17.

机构信息

State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive Disease, Xijing Hospital, Fourth Military Medical University, 127 Changle Western Road, Xi'an 710032, Shaanxi Province, China.

Department of Pediatric Dentistry, School of Stomatology, Fourth Military Medical University, Xi'an 710032, China.

出版信息

Cell Biosci. 2013 Dec 6;3(1):46. doi: 10.1186/2045-3701-3-46.

BACKGROUND

Accumulating evidences have identified the immunoregulatory features of stem cells. In this study, the immunoregulation of bone marrow-derived stem cells (BMSCs) transplanted into patients with HBV-related decompensated cirrhosis and mouse model of liver injury induced by carbon tetrachloride (CCl4) administration was observed.

RESULTS

Compared with healthy controls, patients with HBV-related decompensated cirrhosis showed significantly higher levels of TNF-alpha, IL-12, TGF-beta1, IL-17, and IL-8. However, only IL-17 was markedly decreased after autologous BMSCs transplantation during their follow-up. The same results were found in the CCl4-treated mice. Furthermore, we found that exogenous IL-17 partly abolished the therapeutic effect of BMSCs whereas IL-17-specific antibody promoted improvement of liver injury in CCl4-treated mice, resembling the therapeutic effect of BMSCs transplantation.

CONCLUSIONS

These data suggested that BMSCs transplantation induces a decrease of IL-17 level, which at least in part delineates the mechanisms of stem cells-mediated therapeutic benefit on liver disease.

背景

越来越多的证据表明干细胞具有免疫调节作用。在这项研究中，我们观察了骨髓来源的干细胞（BMSCs）移植入乙型肝炎相关失代偿性肝硬化患者和四氯化碳（CCl4）诱导的肝损伤小鼠模型中的免疫调节作用。

结果

与健康对照组相比，乙型肝炎相关失代偿性肝硬化患者的 TNF-α、IL-12、TGF-β1、IL-17 和 IL-8 水平明显升高。然而，在自体 BMSCs 移植后的随访中，只有 IL-17 明显下降。在 CCl4 处理的小鼠中也得到了相同的结果。此外，我们发现外源性 IL-17 部分消除了 BMSCs 的治疗效果，而 IL-17 特异性抗体促进了 CCl4 处理的小鼠肝损伤的改善，类似于 BMSCs 移植的治疗效果。