Effect of bone marrow mesenchymal stem cell transplantation on senile dementia behaviors

doi:10.3969/j.issn.2095-4344.2016.32.013

Abstract

Abstract:

BACKGROUND: Drug treatment for senile dementia has unsatisfactory outcomes although to a certain extent it can reduce and delay the progression of Alzheimer’s disease. Stem cell transplantation is a new attempt for the treatment of senile dementia.
OBJECTIVE: To observe the effect of bone marrow mesenchymal stem cell transplantation on the behavior of senile dementia rats.
METHODS: Rat models of senile dementia were made in 20 Sprague-Dawley rats that were given continuous 60-day gavage of aluminium chloride solution. Then, model rats were randomized into model group treated with normal saline injection and experimental group treated with hippocampal injection of bone marrow mesenchymal stem cells, respectively. Another 10 rats undergoing normal feeding served as control group. Learning and memory ability of rats were tested by Morris water maze, and superoxide dismutase activity and malondialdehyde content in brain tissues of rats were measured by colorimetric method at 4 weeks after cell transplantation.
RESULTS AND CONCLUSION: Compared with the model group, the escape latency was shortened and the cross-platform frequency was increased in the experimental group (P < 0.05), and moreover, significantly elevated superoxide dismutase activity and reduced malondialdehyde content in the brain tissues of rats were found in the experimental group (P < 0.05). These findings indicate that bone marrow mesenchymal stem cell transplantation contributes to behavior improvement in senile dementia rats by improving the learning and memory ability.

中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Alzheimer Disease, Bone Marrow, Mesenchymal Stem Cell Transplantation, Neurobehavioral Manifestations, Superoxide Dismutase, Malondialdehyde, Tissue Engineering

CLC Number:

R394.2

Gao Ming-long, Sun Li, Zhao Xiao-chuan, Yu Ming, Wang Jin-cheng. Effect of bone marrow mesenchymal stem cell transplantation on senile dementia behaviors[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(32): 4798-4804.

Figures/Tables 2

2.1 实验动物数量分析 SD大鼠30只均进入最终结果分析。 2.2 各组SD大鼠体质量变化应激性造模第1天，各组SD大鼠的体质量差异无显著性意义(P > 0.05)；在应激造模的第15，30，60天，与对照组大鼠比，造模SD大鼠平均体质量偏低，差异有显著性意义(P < 0.05)，结果见表1。骨髓间充质干细胞移植后0周，实验组与模型组比较，体质量差异无显著性意义(P > 0.05)；骨髓间充质干细胞移植后1，2，3，4周，实验组体质量明显高于模型组，差异有显著性意义(P < 0.05)，实验组大鼠体质量越来越接近于对照组，结果见表2。 2.3 各组SD大鼠Morris水迷宫逃避潜伏期测定结果应激性造模第1天，各组大鼠平均逃避潜伏期差异无显著性意义(P > 0.05)，造模第15天，对照组及造模组大鼠逃避潜伏期均明显下降，第30-60天，与对照组相比，造模组的逃避潜伏期均明显较长，差异有显著性意义 (P < 0.05)，见表3。骨髓间充质干细胞移植后0周，实验组与模型组比较，大鼠逃避潜伏期差异无显著性意义(P > 0.05)。移植1，2，3，4周，实验组与模型组比较，实验组平均逃避潜伏期迅速下降，差异有显著性意义 (P < 0.05)，同时实验组大鼠逃避潜伏期越来越接近于对照组，见表4。 2.4 各组大鼠Morris水迷宫跨越平台检测结果与对照组相比，造模成功后SD大鼠跨越平台次数明显减少，差异有显著性意义(P < 0.05)；骨髓间充质干细胞移植后1周，模型组SD大鼠跨越平台次数并没有显著变化，对照组大鼠跨越平台次数略有增加，模型组与对照组比差异有显著性意义(P < 0.05)；实验组与模型组比较，跨越平台次数明显增多，差异有显著性意义(P < 0.05)，但跨越平台次数仍低于对照组，与对照组比较，差异也有显著性意义(P < 0.05)，见表5。 2.5 各组大鼠脑组织超氧化物歧化酶活性及丙二醛水平与对照组比，模型组大鼠脑组织中超氧化物歧化酶活性显著降低(P < 0.05)，而丙二醛水平却明显升高(P < 0.05)。骨髓间充质干细胞移植后，与模型组比较，实验组脑组织中超氧化物歧化酶活性升高(P < 0.05)，丙二醛水平减少(P < 0.05)，与对照组大鼠脑组织中超氧化物歧化酶活性及丙二醛水平相近，见表6。 2.6 体外培养的骨髓间充质干细胞形态分离培养4 h细胞即开始逐渐贴壁，由圆形逐渐变为长梭形(图1)。经流式细胞仪检测CD44、CD90和CD105细胞表型呈阳性表达，CD45细胞表型呈阴性表达(图2)，所分离出的细胞符合骨髓间充质干细胞的形态及表面标志物等特性，具有较好的自我更新能力和多向分化潜能，证实分离所得细胞为骨髓间充质干细胞。 2.7 各组大鼠海马移植部位病理形态学观察对照组大鼠海马细胞结构完整、边缘清晰，细胞层厚、密度大，且排列整齐、紧密(图3A)；模型组大鼠海马细胞结构不完整、与对照组比有大量细胞缺失，细胞层变薄，间隙增大，排列紊乱、疏松(图3B)；实验组骨髓间充质干细胞移植4周后，大鼠海马组织结构基本完整，与模型组比，细胞层增厚，排列整齐(图3C)。"

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