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小鼠骨髓间充质干细胞体内定向诱导分化与治疗肝功能损伤的实验研究
  • ISSN号:0376-2491
  • 期刊名称:《中华医学杂志》
  • 时间:0
  • 分类:R329.2[医药卫生—人体解剖和组织胚胎学;医药卫生—基础医学]
  • 作者机构:[1]东南大学附属中大医院放射科东南大学分子影像实验室,南京210009, [2]东南大学基础医学院病理教研室
  • 相关基金:国家自然科学基金资助项目(30400116);高等学校博士学科点专项科研基金资助项目(20040286037)
中文摘要:

目的 观察小鼠骨髓间充质干细胞(MSC)在肝脏特定微环境下是否向具肝细胞表型与功能的细胞横向分化,并探讨其治疗肝功能损伤的可行性。方法 20只裸小鼠,随机分为4组,每组5只:A组:CCl4与橄榄油1:1混合,按1ml/kg腹腔注射,每周2次。1周后经尾静脉移植1×10^6GFP阳性MSC,术后继续注射CCl4,每周2次;B组:CCl4注射同A组,经尾静脉注入等量生理盐水;C组:正常小鼠,细胞移植同A组;D组:正常对照。术后4周处死全部受试动物,血清检测肝功能,HE、Masson染色行组织学观察,双荧光染色确认GFP阳性细胞并观察其是否表达肝细胞特异性蛋白。结果 A、B组受体肝纤维组织增生显示肝功能损伤模型制作成功,二组胶原分布百分比差异并无统计学意义(10.5±1.5vs12.7±1.6,t=-2.238,P〉0.05)。A组镜下可见GFP阳性细胞主要分布于汇管区及小叶间隔周围,部分同时表达白蛋白(35%±7%);B、C、D组镜下均未见绿色荧光细胞。A组白蛋白水平明显高于B组(24.4g/L±3.3g/Lvs18.6g/L±2.9g/L,P〈0.05),两组血清丙氨酸转氨酶(ALT)水平差异有统计学意义(121U/L±21U/Lvs192U/L±29U/L,P〈0.05)。结论 持续肝功能损伤可以有效诱导MSC向肝迁移增殖,部分MSC在肝细胞持续损伤的微环境下有向肝样细胞横向分化的潜能,提示MSC移植可以在一定程度上修复受损肝功能。

英文摘要:

Objective To observe whether bone mesenehymal stem cells (MSCs) have the potential to transdifferenfiate into functional hepatocyte-like cells in the special "niche" as well as the therapeutic feasibility to repair damaged liver in mice. Methods 20 nude mice were randomly divided into four groups (n =5 in each group) : Group A: 1.0 ml/kg of carbon tetrachloride(CCl4) (dessolved in olive oil by ratio of 1:1 ) was injected into the peritoneum of mice twice a week for 5 weeks. GFP-positive MSCs( 1 ×10^6 cells) were injected into the caudal tail vein 1 week after the first dose of CCl4 ;Group B: treated with CCl4 as in A, but received the same volume of saline ; Group C : normal nude mice with GFP-positive MSCs Transplanted in the same way as in A. Group D : normal controls. 4 weeks after the cell transplantation, all animal subjects were killed. Liver function tests (LFT) , histology of HE and Masson staining as well as double immunofluorescent staining for GFP and albumin were studied in all groups. Results The hepatic fibrosis in group A & B confirmed the success of model for liver damage and there was no marked difference in the percent of the area occupied by collagen between two groups( 10.5 ± 1.5 vs 12. 7 ± 1.6,t = -2. 238 ,P 〉 0. 05). GFP-positive MSCs were mainly observed around portal area or interspace of lobules in group A. Some of GFP-positive cells also express albumin(35% +7% ). While in group B,C or D,there is no such findings. The level of serum albumin in group A was higher than that in group B ( 24. 4 g/L ±3.3 g/L vs 18.6 g/L ±2. 9 g/L,P 〈0. 05) while the level of ALT was also different between two groups ( 121 U/L±21 U/L vs 192 U/L ± 29 U/L, P 〈 0.05 ) . Conclusion The stimulus of persistent liver damage might enhances the migration of MSCs to the liver , in which some of the MSCs have the potential to transdifferentiate into hepatocyte-like cells. Transplantation of MSCs might amend the damaged tissue of host liver to a cert

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期刊信息
  • 《中华医学杂志》
  • 北大核心期刊(2011版)
  • 主管单位:中国科学技术协会
  • 主办单位:中华医学会
  • 主编:
  • 地址:北京市东四西大街42号
  • 邮编:100710
  • 邮箱:nmjc@cma.org.cn
  • 电话:010-85158355 85158180
  • 国际标准刊号:ISSN:0376-2491
  • 国内统一刊号:ISSN:11-2137/R
  • 邮发代号:2-588
  • 获奖情况:
  • 1992年与1996年连续两次在中宣部、国家科委、新闻...,1999年、2003年分别荣获首届国家期刊奖和第二届国...,中国期刊方阵“双高”期刊
  • 国内外数据库收录:
  • 美国化学文摘(网络版),荷兰文摘与引文数据库,荷兰医学文摘,美国生物医学检索系统,日本日本科学技术振兴机构数据库,中国中国科技核心期刊,中国北大核心期刊(2004版),中国北大核心期刊(2008版),中国北大核心期刊(2011版),中国北大核心期刊(2014版),中国北大核心期刊(2000版)
  • 被引量:101941