中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (18): 3243-3246.doi: 10.3969/j.issn.1673-8225.2010.18.004

• 肝移植 liver transplantation • 上一篇    下一篇

输注同基因骨髓间充质干细胞联合脾组织移植诱导肝移植大鼠的免疫耐受

王  谦1,2，李  立2，李晓延2，陈  刚2   

  1. 1昆明医学院，云南省昆明市 650031；2昆明市第一人民医院肝胆胰二科，云南省昆明市  650011
  • 出版日期:2010-04-30 发布日期:2010-04-30
  • 通讯作者: 李 立，教授，主任医师，昆明医学院附属甘美医院肝胆胰二科，云南省昆明市 650011 ynkmlili@yahoo.com
  • 作者简介:王 谦☆，男，1982年生，河南省周口市人，汉族，昆明医学院在读博士，医师，主要从事肝胆胰疾病及肝脏移植的基础和临床工作。 yeswangqian@163.com
  • 基金资助:

    云南省科技厅科研基金资助项目(2007CA007)“多脏器联合移植重大关键技术的研究与应用示范”。

Isogeneic bone marrow mesenchymal stem cells transfusion combined donor spleen tissue transplantation induces allograft tolerance in liver transplant rats

Wang Qian 1, 2, Li Li2, Li Xiao-yan2, Chen Gang2   

  1. 1 Kunming Medical College, Kunming   650031, Yunnan Province, China; 2 Second Department of Hepato-biliary- pancreatic Medicine, First People’s Hospital of Kunming, Kunming  650011, Yunnan Province, China
  • Online:2010-04-30 Published:2010-04-30
  • Contact: Li Li, Professor, Chief physician, Second Department of Hepato-biliary- pancreatic Medicine, First People’s Hospital of Kunming, Kunming 650011, Yunnan Province, China ynkmlili@yahoo.com
  • About author:Wang Qian☆, Studying for doctorate, Physician, Kunming Medical College, Kunming 650031, Yunnan Province, China; Second Department of Hepato-biliary- pancreatic Medicine, First People’s Hospital of Kunming, Kunming 650011, Yunnan Province, China yeswangqian@163.com
  • Supported by:

    the Scientific Research Program of Yunnan Provincial Science and Technology Department, No. 2007CA007*

PDF

460

被引次数

14

摘要：

背景：有研究显示在免疫抑制剂的作用下，同种脾脏细胞移植可诱导免疫耐受，使移植物长期存活。另有研究还显示异种骨髓间充质干细胞移植可延长移植肝存活时间。
目的：观察输注与受体同基因骨髓间充质干细胞联合脾组织移植对诱导大鼠肝移植后免疫耐受的作用。
方法：将受体Lewis大鼠以数字表法随机分为4组：急性排斥组行DA-Lewis大鼠原位肝移植；环孢素A组行DA-Lewis大鼠原位肝移植后灌胃给予环孢素A；干细胞组行DA-Lewis大鼠原位肝移植，同期输注异体Lewis大鼠骨髓间充质干细胞；脾组织移植组在干细胞移植组的基础上同期移植DA大鼠脾组织。观察各组生存期，肝功能情况，血清细胞因子水平，嵌合体的形成情况及肝脏病理变化。
结果与结论：与其他各组相比，脾组织移植组大鼠存活时间明显延长，术后血清丙氨酸氨基转移酶、天冬氨酸氨基转移酶、总胆红素、白细胞介素2、干扰素γ水平明显降低(P < 0.05)，白细胞介素6、白细胞介素10明显升高(P < 0.05)，30 d后受体脾脏中供体阳性细胞明显升高(P < 0.05)。肝脏病理显示，环孢素A组和干细胞组移植肝仅呈急性轻度排斥反应，急性排斥组呈急性重度排斥反应，脾组织移植组未见明显排斥反应。说明大鼠肝脏、脾组织移植后输注同基因骨髓间充质干细胞可减轻移植肝的排斥作用，甚至诱导免疫耐受。

关键词: 嵌合体, 免疫耐受, 骨髓间充质干细胞, 肝移植, 器官移植

Abstract:

BACKGROUND: Studies have shown that isogeneic splenocyte transplantation can induce immune tolerance and prolong liver graft survival under the effect of immunosuppressant. It is reported that bone marrow mesenchymal stem cells (BMSC) transplantation can also prolong the liver graft survival.
OBJECTIVE: To observe the antirejection effect on liver grafts by simultaneous transplantation of isogeneic BMSC and spleen tissue in liver transplant rats.
METHODS: Recipient Lewis rats were randomly divided into 4 groups: in acute rejection group, DA rats as the donor and Lewis rats as the recipients for liver transplantation; in cyclosporine A (CsA) group: recipients received CsA after liver transplantation. In the BMSC group, recipient Lewis rats received simultaneous BMSC transfusion and liver transplantation. In the spleen tissue group, the recipient Lewis rats received DA rat liver, spleen tissue and isogeneic BMSC transplantation. The serum cytokine levels were determined, and liver pathological changes and survival were observed postoperatively. The level of chimerism in the spleen of Lewis rats were also observed.
RESULTS AND CONCLUSION: The blood levels of alanine aminotransferase, aspartate aminotransferase and total bilirubin interleukin-2 (IL-2) and interferon gamma of spleen tissue group were significantly reduced compared with the other groups (P < 0.05), but IL-6 and IL-10 were increased (P < 0.05), and donor positive cells were increased at 30 days (P < 0.05). Liver pathology revealed a mild acute rejection in liver graft of CsA and BMSC groups, severe acute rejection in acute rejection group, but no rejection in spleen tissue transplantation group. Results indicate that isogeneic BMSCs transfusion combined donor spleen tissue transplantation can induce allograft tolerance in liver transplant rats.

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