中国组织工程研究

中国组织工程研究 ›› 2017, Vol. 21 ›› Issue (13): 2068-2073.doi: 10.3969/j.issn.2095-4344.2017.13.017

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

来源于肝纤维化环境内皮祖细胞移植治疗肝纤维化模型大鼠的逆转作用

刘  冉1，兰  玲2，刘博伟2，袁  媛2，秦凌云3，于  静2   

  1. 1河南省荣军医院肿瘤科，河南省新乡市  453003；2郑州大学人民医院消化内科，河南省郑州市  450003；3郑州儿童医院，河南省郑州市  450003
  • 修回日期:2017-01-20 出版日期:2017-05-08 发布日期:2017-06-09
  • 通讯作者: 兰玲，副主任医师，郑州大学人民医院，河南省郑州市 450003
  • 作者简介:刘冉，女，1978年生，河南省新乡市人，汉族，2012年河南大学医学院毕业，硕士，主治医师，主要从事肿瘤的早期干预及治疗研究。
  • 基金资助:

    国家自然科学基金(青年基金)(30900598)；河南省科技厅基础与前沿技术研究项目(142300410380)；河南省卫生厅项目(201303211，082102310088)；河南省科技厅项目(122102310648)

Reversal effect of transplantation of bone marrow-derived endothelial progenitor cells from the liver fibrosis environment in rats with liver fibrosis

Liu Ran1, Lan Ling2, Liu Bo-wei2, Yuan Yuan2, Qin Ling-yun3, Yu Jing2   

  1. 1Oncology Department, Rongjun Hospital of Henan Province, Xinxiang 453003, Henan Province, China; 2Department of Digestion, the People’s Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China; 3Children’s Hospital of Zhengzhou, Zhengzhou 450003, Henan Province, China
  • Revised:2017-01-20 Online:2017-05-08 Published:2017-06-09
  • Contact: Lan Ling, Associate chief physician, Department of Digestion, the People's Hospital of Zhengzhou University, Zhengzhou 450003, Henan Province, China
  • About author:Liu Ran, Master, Attending physician, Oncology Department, Rongjun Hospital of Henan Province, Xinxiang 453003, Henan Province, China
  • Supported by:

    the National Natural Science Foundation of China for the Youth, No. 30900598; the Basic and Cutting-Edge Technology Research Projects of Henan Provincial Science and Technology Department, No. 142300410380; the Project of Henan Provincial Health Department, No. 201303211, 082102310088; the Project of Henan Provincial Science and Technology Department, No. 122102310648

PDF

226

被引次数

1

摘要：

文章快速阅读：

文题释义：
内皮祖细胞移植治疗肝纤维化：内皮祖细胞移植入肝纤维化大鼠体内，大多种植于肝窦状隙、肝门束及纤维间隔内，且集中分布于组织缺血和坏死区域，能明显增强门脉区明胶溶解，促进新生血管形成，辅助肝窦状隙重建，并通过分泌一些细胞因子，发挥促进肝细胞增殖作用，在一定程度上改善肝纤维化。
内皮祖细胞：是内皮细胞的前体，属于多能干细胞，具有强大的血管重建功能，可能有益于纤维化肝组织内的小血管重建和微循环改善，主要存在于骨髓、外周血和脐带血，少量存在于心脏、血管、骨骼肌和脂肪组织。

 

摘要
背景：理论上，从肝纤维化大鼠骨髓中提取经过体内病理环境“筛选”作用后的内皮祖细胞，应更能适应肝纤维化微环境，移植入纤维化肝脏后应更倾向于分化为成熟内皮细胞，参与肝内血管重建。
目的：探讨来源于大鼠肝纤维化体内环境的骨髓源性内皮祖细胞移植对大鼠肝纤维化的治疗作用。
方法：将28只Wistar大鼠随机分为3组：正常组(n=8)皮下注射橄榄油，2次/周；模型组(n=10)皮下注射四氯化碳3 mL/kg，2次/周，首剂加倍，分别于第2，3，5周末尾静脉输注生理盐水；实验组(n=10)皮下注射四氯化碳3 mL/kg，2次/周，首剂加倍，分别于第2，3，5周末尾静脉输注肝纤维化大鼠骨髓源性内皮祖细胞悬液。注射6周末，进行肝功能、凝血功能、肝组织相关蛋白及肝组织病理检查。
结果与结论：①肝组织病理：模型组肝组织呈广泛而严重的肝细胞脂肪变性和坏死，门静脉和中央静脉周围炎症细胞浸润，汇管区扩大及大量纤维组织增生；与模型组相比，实验组肝细胞变性坏死、炎症细胞浸润及纤维组织增生等均有所减轻；②肝组织相关蛋白：与正常组相比，模型组透明质酸、层粘连蛋白和Ⅲ型前胶原、血管内皮生长因子、表皮生长因子水平升高(P < 0.05)；与模型组相比，实验组透明质酸、层粘连蛋白和Ⅲ型前胶原水平明显下降(P < 0.05)，血管内皮生长因子、表皮生长因子水平升高(P < 0.05)；③肝功能、凝血功能：与正常组相比，模型组肝功能、凝血功能严重受损(P < 0.05)；与模型组相比，实验组肝功能明显改善(P < 0.05)；④结果表明：来源于肝纤维化体内环境的骨髓源性内皮祖细胞移植能有效治疗大鼠肝纤维化，其作用机制可能是通过促进肝脏血管新生来实现的。 

 

 

关键词: 干细胞, 移植, 内皮祖细胞, 肝纤维化, 骨髓, 细胞移植, 血管新生, 国家自然科学基金

Abstract:

BACKGROUND: Theoretically, bone marrow-derived endothelial progenitor cells (EPCs) from liver fibrosis rats could be “filtered” by the pathological environment in vivo. These EPCs would be more adapted to the micro-environment of liver fibrosis, and easier to differentiate into mature endothelial cells participating in the intrahepatic vascular remodeling after transplanted into the liver.
OBJECTIVE: To explore the effectiveness of transplantation of bone marrow-derived EPCs from the liver fibrosis environment in liver fibrosis rats.
METHODS: Twenty-eight Wistar rats were randomly divided into three groups as follows: normal group (n=8) were injected with olive oil, twice per week; model group (n=10) were infused with carbon tetrachloride at a dose of 3 mL/kg body weight (double doses for the first time), twice per week, and infused with normal saline through the tail vein at 2, 3 and 5 weeks; EPCs transplantation group (n=10) were infused with carbon tetrachloride at a dose of 3 mL/kg body weight (double doses for the first time), twice per week, and infused with EPCs suspension through the tail vein at 2, 3 and 5 weeks. Six weeks after final injection, the angiogenesis, hepatocyte proliferation and pathological changes in the liver tissues were observed. The liver function and coagulation function were tested.
RESULTS AND CONCLUSION: (1) The pathological changes of the liver: in the model group, fatty degeneration and hepatocyte necrosis in the liver tissue were serious, inflammatory cells were infiltrated around the portal and central vein, the portal areas expanded, and fibrous tissues overgrew. Compared with the model group, these changes were significantly relieved in the EPCs transplantation group (P < 0.05). (2) The expressions of liver-related proteins: compared with the normal group, the levels of hyaluronic acid, laminin, type III procollagen, vascular endothelial growth factor, epidermal growth factor were significantly increased in the model group (P < 0.05). Compared with the model group, the levels of hyaluronic acid, laminin and type III procollagen were decreased significantly (P  < 0.05), and the levels of vascular endothelial growth factor and epidermal growth factor were increased in the EPCs transplantation group (P  < 0.05). (3) Liver function and coagulation function: compared with the normal group, the liver function and blood blotting function of rats were seriously damaged in the model group (P  < 0.05). Compared with the model group, the liver function and coagulation function were obviously improved in the EPCs transplantation group (P  < 0.05). To conclude, transplantation of bone marrow-derived EPCs from the liver fibrosis environment is effective for liver fibrosis in rats. The mechanism may be associated with the promotion of angiogenesis in the liver.

 

 

Key words: Stem Cells, Liver Cirrhosis, Tissue Engineering

中图分类号: