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人脐带间充质干细胞的肝向分化潜能:对肝纤维化/肝硬化的治疗作用。

hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells: Therapeutic effect on liver fibrosis/cirrhosis.

机构信息

Department of Gastroenterology, The Second Hospital of Hebei Medical University, Shijiazhuang 050000, Hebei Province, China.

出版信息

World J Gastroenterol. 2017 Dec 14;23(46):8152-8168. doi: 10.3748/wjg.v23.i46.8152.

Abstract

AIM

To investigate the hepatic differentiation potential of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) and to evaluate their therapeutic effect on liver fibrosis/cirrhosis.

METHODS

A CCl-induced liver fibrotic/cirrhotic rat model was used to assess the effect of hUC-MSCs. Histopathology was assessed by hematoxylin and eosin (H&E), Masson trichrome and Sirius red staining. The liver biochemical profile was measured using a Beckman Coulter analyzer. Expression analysis was performed using immunofluorescent staining, immunohistochemistry, Western blot, and real-time PCR.

RESULTS

We demonstrated that the infused hUC-MSCs could differentiate into hepatocytes . Functionally, the transplantation of hUC-MSCs to CCl-treated rats improved liver transaminases and synthetic function, reduced liver histopathology and reversed hepatobiliary fibrosis. The reversal of hepatobiliary fibrosis was likely due to the reduced activation state of hepatic stellate cells, decreased collagen deposition, and enhanced extracellular matrix remodeling the up-regulation of MMP-13 and down-regulation of TIMP-1.

CONCLUSION

Transplanted hUC-MSCs could differentiate into functional hepatocytes that improved both the biochemical and histopathologic changes in a CCl-induced rat liver fibrosis model. hUC-MSCs may offer therapeutic opportunities for treating hepatobiliary diseases, including cirrhosis.

摘要

目的

研究人脐带间充质干细胞(hUC-MSCs)的肝向分化潜能,并评估其对肝纤维化/肝硬化的治疗作用。

方法

采用 CCl 诱导的肝纤维化/肝硬化大鼠模型来评估 hUC-MSCs 的作用。通过苏木精和伊红(H&E)、Masson 三色和天狼猩红染色评估组织病理学。使用贝克曼库尔特分析仪测量肝生化特征。采用免疫荧光染色、免疫组化、Western blot 和实时 PCR 进行表达分析。

结果

我们证明了输注的 hUC-MSCs 可以分化为肝细胞。功能上,将 hUC-MSCs 移植到 CCl 处理的大鼠中,可改善肝转氨酶和合成功能,减轻肝组织病理学变化,并逆转肝胆纤维化。肝胆纤维化的逆转可能归因于肝星状细胞的激活状态降低、胶原沉积减少以及细胞外基质重塑增加,导致 MMP-13 上调和 TIMP-1 下调。

结论

移植的 hUC-MSCs 可以分化为功能性肝细胞,改善 CCl 诱导的大鼠肝纤维化模型中的生化和组织病理学变化。hUC-MSCs 可能为治疗肝胆疾病(包括肝硬化)提供治疗机会。

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