Effects of brain-derived neurotrophic factor-modified human amniotic membrane-derived mesenchymal stem cell transplantation on learning and memory abilities of Alzheimer's disease rats

doi:10.3969/j.issn.2095-4344.0474

Abstract

Abstract:

BACKGROUND: A variety of stem cells have been found to be effective in the treatment of Alzheimer's disease in rats. However, few reports have been reported on the treatment of Alzheimer's disease rats with brain-derived neurotrophic factor (BDNF)-modified human amniotic membrane-derived mesenchymal stem cells.
OBJECTIVE: To investigate the effects of BDNF-modified human amniotic membrane-derived mesenchymal stem cell transplantation on the learning and memory abilities of Alzheimer's disease rats.
METHODS: Forty-eight Sprague-Dawley rats were divided into control group (no treatment), model group (Alzheimer's disease model), stem cell transplantation group (human amniotic membrane-derived mesenchymal stem cell transplantation+Alzheimer's disease model) and BDNF-modified stem cell transplantation group (BDNF-modified human amniotic membrane-derived mesenchymal stem cell transplantation+Alzheimer's disease model), 12 rats in each group. Learning and memory of model rats were determined in a trisection radiation maze and immunohistochemical staining was used to determine the number of p75 positive neurons at 2 weeks after cell transplantation.
RESULTS AND CONCLUSION: The number of p75 positive neurons in the bevel zone and medial septal nucleus was ranked as follows: the model group < the stem cell transplantation group < the BDNF-modified stem cell transplantation group < the control group, and there were significant differences among groups (P < 0.05). The learning and memory abilities of the rats were ranked as follows: the model group < the stem cell transplantation group < the BDNF-modified stem cell transplantation group < the control group, and there were significant differences among groups (P < 0.05). In the BDNF-modified stem cell transplantation group, the number of learnings was negatively correlated with the number of p75 NGFR-positive neurons (P < 0.05), while the memory capacity was positively correlated with the number of p75 NGFR-positive neurons (P < 0.05). These findings reveal that human amniotic membrane-derived mesenchymal stem cell transplantation can improve learning and memory abilities of Alzheimer's disease rats, and BDNF-modified human amniotic membrane-derived mesenchymal stem cells can further improve this therapeutic effect.

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: Amnion, Mesenchymal Stem Cell Transplantation, Brain-Derived Neurotrophic Factor, Alzheimer Disease, Learning, Memory, Receptor, Nerve Growth Factor, Tissue Engineering

CLC Number:

R394.2

Gao Ming-long, Shi Shao-xia, Zhang Kun, Zhang Ying-dong, Li Na, Yu Ming, Wang Yong-liang. Effects of brain-derived neurotrophic factor-modified human amniotic membrane-derived mesenchymal stem cell transplantation on learning and memory abilities of Alzheimer's disease rats[J]. Chinese Journal of Tissue Engineering Research, 2018, 22(9): 1419-1424.

Figures/Tables 2

2.1 人羊膜间充质干细胞的形态培养12 h开始少量贴壁生长；培养24 h贴壁生长细胞增多(图1A)；培养72 h时贴壁细胞明显增多，细胞呈三角形、放射状或短梭状生长(图1B)；培养7 d细胞呈纺锤形或梭形成纤维细胞样生长，形成细胞克隆集落(图1C)。原代培养12 d贴壁细胞长满瓶底，呈长梭形、形态均一，漩涡状排列，达85%融合，经消化后进行传代。传代培养24 h细胞呈长梭形、完全贴壁生长；传代培养72 h细胞呈漩涡样排列，融合达80%以上；传代培养7 d细胞完全融合(图1D)，继续再次传代培养。 2.2 流式细胞仪检测人羊膜间充质干细胞表面标记第3代人羊膜间充质干细胞表面高表达CD44、CD29、CD105、CD90分子，阴性表达CD34、CD31和CD45分子。 2.3 各组大鼠p75 NGFR阳性神经元数目比较各组大鼠斜角带和内侧隔核p75 NGFR阳性神经元数比较差异有显著性意义(P < 0.05)，其中模型组、干细胞移植组、BDNF修饰干细胞移植组斜角带和内侧隔核p75 NGFR阳性神经元数均低于对照组(P < 0.05)，干细胞移植组、BDNF修饰干细胞移植组斜角带和内侧隔核p75 NGFR阳性神经元数均高于模型组(P < 0.05)，BDNF修饰干细胞移植组斜角带和内侧隔核p75 NGFR阳性神经元数高于干细胞移植组 (P < 0.05)。见表1，图2，3。 2.4 各组大鼠学习记忆能力比较各组大鼠的学习记忆能力比较差异有显著性意义(P < 0.05)，其中模型组、干细胞移植组、BDNF修饰干细胞移植组大鼠的学习记忆能力均低于对照组(P < 0.05)，干细胞移植组、BDNF修饰干细胞移植组大鼠的学习记忆能力均高于模型组(P < 0.05)，BDNF修饰干细胞移植组大鼠的学习记忆能力高于干细胞移植组(P < 0.05)。见表2。 2.5 BDNF修饰干细胞移植组大鼠的学习记忆能力与p75 NGFR阳性神经元数的相关性分析 BDNF修饰干细胞移植组大鼠的学习次数与p75 NGFR阳性神经元数呈负相关(P < 0.05)，记忆能力与p75 NGFR阳性神经元数呈正相关(P < 0.05)。见表3。"

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