中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (6): 1048-1052.doi: 10.3969/j.issn.1673-8225.2010.06.020

• 干细胞移植 • 上一篇    下一篇

异体脐带间充质干细胞对大鼠心脏移植的免疫调节

刘奎利,刘德忠,金建刚,李海斌,史迎昌,黎  立,韩  勇,许晓光,石炳毅   

  1. 解放军总医院第二附属医院器官移植中心,北京市 100091
  • 出版日期:2010-02-05 发布日期:2010-02-05
  • 通讯作者: 石炳毅,硕士,教授,主任医师,博士生导师,解放军总医院第二附属医院器官移植中心,北京市 100091 shibingyi@medmail.com.cn
  • 作者简介:刘奎利,男,1975年生,吉林省辽源市人,汉族,解放军军医进修学院在读博士,主治医师,主要从事泌尿外科及器官移植方面的研究。 liukuili1975@163.com
  • 基金资助:

    全军“十一五”计划科研项目资助课题(06G115),课题名称“器官移植免疫调节的临床与基础研究”;
    国家科技支撑计划课题(2008BAI60B04),课题名称“抗排斥反应关键诊疗技术的开发研究”。

Immunomodulatory effects of xenogenous umbilical cord mesenchymal stem cells on rat heart transplantation

Liu Kui-li, Liu De-zhong, Jin Jian-gang, Li Hai-bin, Shi Ying-chang, Li Li, Han Yong, Xu Xiao-guang, Shi Bing-yi   

  1. Organ Transplantation Center, Second Affiliated Hospital of General Hospital of Chinese PLA, Beijing   100091, China
  • Online:2010-02-05 Published:2010-02-05
  • Contact: Shi Bing-yi, Master, Professor, Chief physician, Doctoral supervisor, Organ Transplantation Center, Second Affiliated Hospital of General Hospital of Chinese PLA, Beijing 100091, China shibingyi@medmail.com.cn
  • About author:Liu Kui-li, Studying for doctorate, Attending physician, Organ Transplantation Center, Second Affiliated Hospital of General Hospital of Chinese PLA, Beijing 100091, China liukuili1975@163.com
  • Supported by:

    the Scientific Research Project during the 11th Five-Year Plan Period of Chinese PLA, No.06G115*;
    the National Technology Supporting Project, No.2008BAI60B04*

摘要:

背景:有资料表明骨髓间充质干细胞可延长小鼠和狒狒异体皮肤移植存活时间,降低造血干细胞移植后急性和慢性移植物抗宿主病的发生,但目前尚未见关于大鼠脐带间充质干细胞用于心脏移植减少排斥反应的报道。

目的:观察异体脐带间充质干细胞对大鼠心脏移植的免疫调节作用。

方法:DA大鼠20只作为供体,Lewis大鼠20只作为受体,均随机分为2组,即药物干预组、对照组,每组供受体大鼠各10只。采用双套管法将供体大鼠的左肺动脉和无名动脉分别与受体大鼠心脏的颈外静脉和颈总动脉在显微镜下行端端吻合,建立异位心脏移植模型。Wistar孕鼠1只,采用胶原酶消化法分离培养脐带间充质干细胞。造模后,细胞移植组经尾静脉注射脐带间充质干细胞,对照组同法注射氯化钠注射液。检测移植心脏的存活时间,采用心脏移植急性排斥反应诊断标准对移植心脏进行组织病理学评分,苏木精-伊红染色观察移植心脏淋巴细胞浸润程度。

结果与结论:与对照组比较,细胞移植组移植心脏存活时间显著延长(P=0.001),急性排斥反应病理学评分显著降低(P=0.000 4)。对照组心肌组织内有大量淋巴细胞和单核细胞浸润,细胞移植组心肌组织内有少量淋巴细胞浸润,心肌间质轻度水肿。结果证实大鼠脐带间充质干细胞可诱导心脏移植免疫耐受,减轻免疫排斥反应,延长心脏存活时间。

关键词: 免疫调节, 心脏移植, 大鼠, 脐带, 间充质干细胞

Abstract:

BACKGROUND: Bone marrow mesenchymal stem cells (BMSCs) can prolong the survival time of mice and baboons’ alloskin graft and degrade acute and chronic graft-versus-host disease (GVHD) incidence after hematopoietic stem cell transplantation. But, at present there is no report that rat umbilical cord mesenchymal stem cells (UC-MSCs) reduced rejection response following heart transplantation.

OBJECTIVE: To study the immunomodulatory effects of rat UC-MSCs on a model of allogeneic heart transplantation.

METHODS: A total of 20 DA rats served as donors, and 20 Lewis rats as recipients. They were equally and randomly assigned to 2 groups: drug intervention and control groups (n=10). Using double cannulation, the left pulmonary artery and innominate artery of rat donors and external jugular vein and common carotid artery of rat recipients received end-to-end anastomosis under a microscope to establish heterotopic cardiac transplantation. One Wistar pregnant rat was selected to harvest UC-MSCs by collagenase digestion method. Following model establishment, rats in the cell transplantation group received UC-MSCs via caudal vein. Rats in the control group received sodium chloride. Survival time of the transplanted heart was determined. The transplanted heart received histopathology score using the acute rejection diagnosis criteria. Lymphocyte infiltration of transplanted heart was observed using hematoxylin-eosin staining.

RESULTS AND CONCLUSION: Compared with the control group, the survival time of the transplanted heart was significantly longer in the cell transplantation group (P = 0.001), and the pathological score of acute rejection was significantly reduced (P = 0.000 4). There were lots of lymphocyte and monocyte infiltration in the myocardium in the control group. Little lymphocyte infiltration was detected in the myocardium in the cell transplantation group, with the presence of mild edema of myocardial interstitial substance. Results verified that rat UC-MSCs can induce immune tolerance of heart transplantation, soften immunological rejection and prolong xenograft survival.

中图分类号: