中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (14): 2560-2563.doi: 10.3969/j.issn.1673-8225.2010.14.018

• 干细胞移植 stem cell transplantation • 上一篇    下一篇

骨髓间充质干细胞肝中叶注射移植治疗新西兰大白兔肝脏衰竭

凌霄华1，胡成乙2，洪  钰1，于  欣1，米丽娜1，杨小明1   

  1. 哈尔滨医科大学附属第四医院，  1消化内科；2病理科，黑龙江省哈尔滨市  150001
  • 出版日期:2010-04-02 发布日期:2010-04-02
  • 作者简介:凌霄华★，女，1971年生，黑龙江省哈尔滨市人，汉族，2006年哈尔滨医科大学毕业，硕士，主治医师，主要从事消化系统疾病的研究。 lingxh_2008@hotmail.com
  • 基金资助:

    黑龙江省卫生厅科研课题(2007-414)。

Bone marrow-derived mesenchymal stem cells injection for liver failure in New Zealand white rabbits

Ling Xiao-hua1, Hu Cheng-yi2, Hong Yu1, Yu Xin1, Mi Li-na1, Yang Xiao-ming1   

  1. 1 Department of Digestive System, 2 Department of Pathology, Fourth Hospital of Harbin Medical University, Harbin   150001, Heilongjiang Province, China
  • Online:2010-04-02 Published:2010-04-02
  • About author:Ling Xiao-hua★, Master, Attending physician, Department of Digestive System, Fourth Hospital of Harbin Medical University, Harbin 150001, Heilongjiang Province, China lingxh_2008@hotmail.com
  • Supported by:

    the Scientific Research Program of Heilongjiang Department of Health, No. 2007-414*

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摘要：

背景：肝细胞移植作为治疗肝脏衰竭的一种有效方法在各种动物模型及临床应用中得到广泛证实，但供体短缺及移植肝细胞增殖困难等问题严重困扰着肝细胞移植的发展。研究表明骨髓间充质干细胞具有向肝细胞及胆管上皮细胞双向分化的潜能，而且具有强大的增殖能力，它作为一种新的细胞来源为解决上述难题提供了新思路。
目的：以肝中叶注射移植骨髓间充质干细胞治疗新西兰大白兔肝脏衰竭，验证其效果。
方法：健康雄性新西兰大白兔给予D-氨基半乳糖24 h后，移植组于肝中叶注射骨髓间充质干细胞悬液3 mL(1×109 L-1)，对照组注射相同体积不含骨髓间充质干细胞的培养液。移植后48 h、72 h、1周、4周取外周血测定谷丙转氨酶、谷草转氨酶活性，移植后4周取肝脏做病理检测。
结果与结论：移植后新西兰大白兔肝功能指标明显下降，在第4周时移植组谷丙转氨酶、谷草转氨酶活性明显低于对照组   (P < 0.05)。移植后4周对照组表现为肝索紊乱，肝细胞肿胀变性、灶性及大片坏死，伴出血及炎性细胞浸润。移植组显示肝小叶结构可辨认，点状坏死肝细胞间再生肝细胞较前增多，汇管区、中央静脉及坏死灶周围可见核/浆比例较大的小细胞，并向肝组织内延伸，可见灶性增生。

关键词: 肝脏衰竭, 大白兔, 病理, 肝功能, 骨髓间充质干细胞

Abstract:

BACKGROUND: Hepatocyte transplantation as an effective method for liver failure has been confirmed by animal models and clinical application. However, limited source and poor proliferation of hepatocyte graft limit its development. Studies have shown that bone marrow mesenchymal stem cells (MSCs) have potentials to differentiate into hepatocyte and bile epithelial cells, with strong proliferation.
OBJECTIVE: To explore the therapeutic effect of bone marrow MSCs transplantation on liver failure of New Zealand white rabbits.
METHODS: Adult male New Zealand rabbits were treated with D-galactosamine, and 3 mL hepatocyte suspension (1×109 /L) was injected into the liver of transplantation group, but the control group was injected with the same volume of culture solution with no bone marrow MSCs. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was detected 48, 72 hours, 1, 4 weeks following transplantation, and pathological detection was performed at 4 weeks.
RESULTS AND CONCLUSION: The liver functional index following transplantation of bone marrow-derived MSCs transplantation was significantly decreased, and ALT and AST activity at 4 weeks was significantly less than the control group (P < 0.05). At 4, the transplantation group displayed disorderly hepatic cord, hepatocyte swollen and degeneration, necrosis, accompanied by bleeding and inflammatory cell infiltration. In addition, the hepatic lobule structure was detectable, and regenerative hepatocyte increased among necrotic hepatocyte; small cells with large ratio of nucleus and cytoplasm at header, central vein and surrouding necrosis focus extended to the liver tissues.

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