中国组织工程研究

中国组织工程研究 ›› 2010, Vol. 14 ›› Issue (40): 7453-7457.doi: 10.3969/j.issn.1673-8225.2010.40.010

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

人骨髓间充质干细胞移植老年性痴呆大鼠认知能力和海马超微结构的变化

何  炜1，薄  海2，牟心红2，张  岭3，李海生2　   

  1. 武警医学院，1附属医院，2基础部，3预防医学系，天津市  300162
  • 出版日期:2010-10-01 发布日期:2010-10-01
  • 通讯作者: 李海生，博士，副教授，武警医学院基础部，天津市 300162 lihaisheng65@yahoo.com.cn
  • 作者简介:何炜★，男，1977年生，河北省保定市人，汉族，2007年天津医科大学毕业，硕士，讲师，主要从事急诊临床方面的研究。shinehwbx@163.com
  • 基金资助:

    天津市应用基础研究计划项目(07JCYBJC08200)，课题名称“骨髓间充质干细胞分化及移植治疗AD大鼠的应用基础研究”。

Effects of human bone marrow mesenchymal stem cell transplantation on cognitive ability and hippocampus ultrastructure in Alzheimer’s disease rats

He Wei1, Bo Hai2, Mu Xin-hong2, Zhang Ling3, Li Hai-sheng2　   

  1. 1 Affiliated Hospital, 2 Basic Department, 3 Departmeat of Preventive Medicine, Medical College of Chinese People’s Armed Police Force, Tianjin  300162, China
  • Online:2010-10-01 Published:2010-10-01
  • Contact: Li Hai-sheng, Doctor, Associate professor, Basic Department, Medical College of Chinese People’s Armed Police Force, Tianjin 300162, China lihaisheng65@yahoo.com.cn
  • About author:He Wei★, Master, Lecturer, Affiliated Hospital, Medical College of Chinese People’s Armed Police Force, Tianjin 300162, China shinehwbx@163.com
  • Supported by:

    the Application and Basic Research Project of Tianjin City, No. 07JCYBJC08200*

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摘要：

背景：因发病机制不明，目前尚无治愈老年性痴呆的有效方法。现临床上主要是采用药物治疗，而骨髓间充质干细胞的替代治疗尚处于基础研究阶段，其海马移植后对老年性痴呆认知能力的影响未见报道。
目的：探讨人骨髓间充质干细胞移植对老年性痴呆大鼠认知能力和海马超微结构的影响。
方法：老年雄性Wistar大鼠30只，制备自然衰老痴呆模型，造模后随机分为3组，选取双侧海马为移植区，分化细胞移植组注射定向神经细胞诱导分化的人骨髓间充质干细胞悬液4 μL(2×105个细胞)，干细胞移植组注射等量常规培养的人骨髓间充质干细胞，模型组注射等量生理盐水。通过Y迷宫试验测定大鼠的学习、记忆能力，透射电镜观察海马区超微结构。
结果与结论：与移植前大鼠学习、记忆分数比较，移植后12周模型组均显著下降(P < 0.01)，干细胞移植组均有所提高(P > 0.05)，分化细胞移植组均显著提高(P < 0.01)。移植后12周与模型组比较，干细胞移植组、分化细胞移植组大鼠学习、记忆分数均显著提高(P < 0.01)。电镜观察模型组大鼠海马区神经细胞可见明显损伤，干细胞移植组损伤减轻，分化细胞移植组多数神经细胞结构正常。证实骨髓间充质干细胞移植可以提高老年性痴呆大鼠的认知能力，且定向神经诱导分化的骨髓间充质干细胞移植治疗效果优于未分化的骨髓间充质干细胞，提示骨髓间充质干细胞减少海马组织神经细胞变性坏死可能是其改善老年性痴呆大鼠认知功能障碍的作用机制之一。

关键词: 老年性痴呆, 认知能力, 海马, 细胞移植, 骨髓间充质干细胞

Abstract:

BACKGROUND: There is no effective method to treat Alzheimer’s disease, due to unclear onset mechanism. In clinic, drug therapy is commonly used, but replacement therapy of bone marrow mesenchymal stem cells (BMSCs) remains in basic research stage. There is no report concerning effects of BMSC transplantation in the hippocampus on cognitive ability of Alzheimer’s disease.
OBJECTIVE: To investigate the effects of BMSC transplantation on cognitive ability and hippocampus ultrastructure in Alzheimer’s disease rats.
METHODS: A total of 30 senile male Wistar rats with Alzheimer’s disease were chosen to prepare models of natural senescence Alzheimer’s disease. Following model establishment, the rats were assigned to three groups. Bilateral hippocampi were selected as transplantation region. In the differentiation and transplantation group, rats received injection of neuronal induced BMSCs 4 μL (2×105 cells). In the BMSC transplantation group, rats received an equal volume of human BMSCs. In the model group, rats were injected bilaterally with physiological saline into the hippocampus. The learning and memory ability of the rats were detected by Y type maze test. The hippocampus ultrastructure was observed with transmission electron microscopy.
RESULTS AND CONCLUSION: The learning and memory scores significantly decreased in model group (P < 0.01), increased in BMSC transplantation group (P > 0.05), and significantly increased in the differentiation and transplantation group (P < 0.01). On week 12, compared with model group, the learning and memory scores were significantly higher in BMSC transplantation group and differentiation and transplantation group (P < 0.01). With the electron microscopy, hippocampus neurons were obviously injured in model group, but the majority of neurons were injured mildly in BMSC transplantation group, which the majority of them were almost normal in differentiation and transplantation group. These indicated that BMSC transplantation may improve the cognitive ability of Alzheimer’s disease rats, and neuronal induced BMSC transplantation is superior to undifferentiated BMSCs. Lowering hippocampus neuronal necrosis may be one of mechanisms that BMSCs improve cognitive dysfunction in Alzheimer’s disease rats.

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