脐带间充质干细胞移植对慢性试验性肝损伤的治疗作用  

Umbilical cord mesenchymal stem cell for chronic experimental liver injury

作　　者：赵钦军[1] 任红英[1] 池颖[1] 韩之波[1] 马凤霞[1] 陈芳[1] 卢士红[1] 韩忠朝[1] 

机构地区：[1]中国医学科学院北京协和医学院血液学研究所(血液病医院)实验血液学国家重点实验室,天津300020

出　　处：《中华细胞与干细胞杂志（电子版）》2014年第4期20-25,共6页Chinese Journal of Cell and Stem Cell（Electronic Edition）

基　　金：国家重点基础研究发展计划(973计划:2011CB964802);国家自然科学基金(81000196;81330015);天津市应用基础及前沿技术研究计划(12JCZDJC25000)

摘　　要：目的观察脐带间充质干细胞(UC-MSC)对慢性实验性肝损伤的治疗作用并探讨其分子生物学机理。方法 50只7周龄的NOD/SCID小鼠注射四氯化碳(CCL4)制备慢性肝损伤模型后,应用随机数字表的方法随机将实验小鼠随机分成2组:模型组(25只)和UC-MSC移植组(25只)。UC-MSC移植组通过尾静脉注射移植1×106 UC-MSC,模型组注射同样体积的PBS。分别于移植后1、2、3和4周收集肝组织,应用免疫组织化学,RT-PCR和Western blot的方法分析细胞移植前后肝组织的病理生理学特征的变化。采用t检验和方差分析进行统计学分析。结果 UC-MSC移植治疗后肝组织表达人肝细胞特异性AFP,Alb,和内皮细胞特异性CD31,Flk-1。细胞移植4周后v WF标记的血管密度明显增加,同时伴有部分的肝功能改善,谷丙转氨酶(ALT)水平从(55.71±11.33)U/L减至(36.75±12.80)U/L(P<0.05)。此外,本研究结果表明UC-MSC分泌几种重要的生长因子HGF,FGF-2,VEGF,和VEGF受体通过旁分泌的途径发挥肝组织修复的功能。结论在CCL4诱导的慢性肝损伤模型肝组织,人UC-MSC可以分化成肝细胞样细胞和内皮细胞样细胞,同时旁分泌多种细胞生长因子修复损伤的肝细胞,并伴有肝功能的改善。认为UCMSC移植或许成为将来肝脏损伤疾病一个重要的治疗选择。Objective Recent observations indicate that mesenchymal stem cells （MSC） derived from many tissues can differentiate into hepatocytes in vitro. It is also reported that MSC can be used to treat liver disease in animal models. However, there are different conclusions from different research groups, and the mechanisms are still not clear. Methods Fifty 7-week-old NOD / SCID mice were injected by carbon tetrachloride （CCL4） to induce chronic liver injury model. Mice were randomly divided into two groups： model group （25） and UC-MSC transplantation group （25）. One, 2, 3 and 4 weeks after 1 ×10^6 UC-MSC transplanted by tail vein infusion, liver tissue were collected. In addition, immunohistochemistry, RT-PCR and Western blot analysis were used to characterize pathophysiology of liver tissue. T-test and ANOVA was used for statistical analysis. Results Liver cell-specific human AFP, Alb, and endothelial cell-specific CD31, Flk-1 was expressed in liver tissue after UC-MSC infusion. Vascular density marked by vWF significantly increased at 4 weeks after cell infusion. And there is significant improvement in liver function. Furthermore, our results indicate that UC-MSC secreted several important growth factors including HGF, FGF-2, and VEGF in liver tissue after cell infusion. Conelusions Human UC-MSC can differentiate into hepatocyte- like cells and endothelial-like cells in CCL4-induced chronic liver injury tissue. UC-MSC also paracrine a variety of cell-growth factors to repair damaged liver cells, resulting in liver function improvement. UC-MSC infusion may become an important therapeutic option for liver damage in future.

关 键 词：脐带 间充质干细胞 肝损伤 肝细胞 细胞移植 

分 类 号：R575.3[医药卫生—消化系统]