骨髓间质干细胞肝向诱导分化前后肝功能代偿能力的比较  

Comparative Study on the Effects on Restoring Hepatic Functions by Transplantation of Hepatic Induced Bone Marrow Stromal Cells in Different Differentiated State

作　　者：刘芳[1,2] 陈少红[2] 刘青波[2] 范新娟[2] 唐芳[2] 刘大伟[2] 赵国强[2] 

机构地区：[1]南华大学医学院病理学教研室,湖南衡阳421001 [2]中山大学附属第一医院病理科

出　　处：《中南医学科学杂志》2011年第3期246-249,257,共5页Medical Science Journal of Central South China

基　　金：国家自然科学基金资助(No.30170473);广东省自然科学基金资助(No.04009326);湖南省教育厅课题资助(No.08C744);肿瘤细胞与分子病理学湖南省高校重点实验室资助;湖南省高校创新平台开放基金资助(No.09K074;09K075)

摘　　要：目的探讨不同分化状态骨髓间质干细胞移植对急性肝功能衰竭大鼠的肝功能重建的影响,并进行综合比较评估。方法以D-氨基半乳糖胺(D-gal)构建的雌性大鼠急性肝衰竭模型后大鼠,随机分为4组:BMSCs移植组,幼稚肝细胞移植组,成熟肝细胞移植组和空白对照组,结合多项血生化指标对不同分化阶段BMSCs的肝功能代偿能力进行综合评估。并以sry基因为分子标志,采用PCR技术检测植入细胞在受体动物体内的存留状态及定位情况。结果各组肝衰模型动物经细胞移植后,所测各项血清生化指标均有显著变化。血清谷丙转氨酶(ALT)、谷草转氨酶(AST)、总胆红素(TBIL)的水平明显下降,白蛋白(ALB)的水平有所上升。各移植组之间相比,诱导至成熟肝细胞状态的细胞无论对肝功能的改善或是降低动物死亡率,效果均为最优。细胞移植后的第30天,仍能在受体动物肝脏内检查到sry基因信号。结论体外诱导分化至不同阶段的BMSCs均能在一定程度上代偿衰竭肝脏的功能,而诱导分化至成熟状态的细胞对肝功能的代偿能力最强,可作为代偿肝功能的重要细胞源之一。Objective To explore the effects on restoring hepatic functions of acute hepatic failure model rat by transplantation of hepatic induced bone marrow stromal cells （ BMSCs ） in different differentiated state. Methods Dgalactosamine （D-gal） was served as hepatic toxic agent,female SD rats with acute hepatic failure model were randomly divided into 4 groups ： BMSCs transplantation group, mature hepatocyte-like cells transplantation group, immature hepatocytelike cells transplantation group and control group. The compensatory ability of hepatic functions of the transplanted cells was evaluated according to the changes of biochemical markers in serum, and sty gene was tested in the liver and lung of the re- ceiver rat by PCR technique. Results There are distinct changes of the tested serum biochemical markers of acute hepatic failure model rat after cell transplantation. The serum levels of ALT, AST, and TBIL were distinctly descended, and the level of ALB was ascended. The ability of improving hepatic function and depressing mortality of the mature induced hapatocyte-like cells is the best among all the cell transplantation groups. The signal of sty gene can be detected in the liver of the receiver rat till 30 days after cell transplantation. Conclusions Both the in vitro hepatic induced differentiated BMSCs（immature induced and mature induced） and the non-induced BMSCs have a compensatory ability of the prostrate hepatic functions. However, the ability of the mature induced hapatocyte-like cells to improve hepatic function and to depress mortality is better than that of immature differentiated cells as well as non-induced BMSCs, and may be first selected as a cell source of cell transplantation.

关 键 词：骨髓间质干细胞 定向分化 肝衰竭 细胞移植 

分 类 号：R329.2[医药卫生—人体解剖和组织胚胎学]