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学科主题: 神经生物学
题名:
神经干细胞在圆柱体上的分化研究及其联合神经营养因子和聚醚酯/多肽水凝胶在脑卒中治疗方面的探索
作者: 闫东东
答辩日期: 2016-05-11
导师: 万峻
专业: 神经生物学
授予单位: 北京大学
授予地点: 北京大学深圳医院
学位: 硕士
关键词: 神经干细胞 ; 微型圆柱体 ; 分化率 ; 直径 ; 间距 ; 缺血再灌注损伤 ; 聚醚酯/多肽水凝胶 ; NT-3 NGF BDNF ; 炎症
其他题名: Exploration of differentiation of neural stem cells (NSCs) on micropillar silicon substrate and therapy of stroke with NSCs, neurotrophins and Polyester-Polyether Bearing Pendant Azide/ Polypeptide Hydrogel
分类号: R329.2
摘要:

利用神经干细胞移植治疗中枢神经系统疾病一直是研究的热点,但如何调控神经干细胞的定向分化则是决定此方法能否运用到临床治疗的关键问题。除了生物化学因子等因素外,生物物理信号也能够调节神经干细胞的分化。本课题第一部分中,我们探索了单晶硅表面的微型形态结构对于小鼠原代神经干细胞分化的影响。单晶硅表面排列着多种圆柱体,直径和间距都在2.5μm到20μm之间。研究发现,直径较小且间距较大的微型圆柱体能够有效的促进神经干细胞分化为神经元样细胞。随着微型圆柱体直径的减小,神经干细胞分化为神经元样细胞的比例逐渐增加,但随着其圆柱体间距的减小,其分化为神经元样细胞的比例逐渐降低。这对于研发组织工程支架材料表面结构属性有着重要的提示作用。本课题第二部分,我们利用温敏的聚醚酯/多肽水凝胶吸附三种神经营养因子,检测其缓释效果,与此同时,我们将其与培养的神经干细胞悬液混和,原位注入大鼠脑缺血再灌注损伤区。饲养60天,同时对损伤后大鼠的行为学进行检测,评估其治疗效果,并探讨其内在机制。结果发现神经干细胞、神经营养因子和聚醚酯/多肽水凝胶联合治疗的效果优于其他各对照组,三种成分治疗效果的大小顺序为:神经干细胞>神经营养因子,神经干细胞>聚醚酯/多肽水凝胶。这种治疗策略能有效的控制炎症反应可能是促进大鼠行为功能恢复的机制。

英文摘要:

Neural stem cells (NSCs) has been hot as a therapy of central neural system injuries in these years. Whether we could manipulate its neuron-oriented differentiation, however, is a critical factor affecting its clinical treatment application. Besides all kinds of biochemical factors that regulate NSCs differentiation, biophysical signal can have an effect as well. In the first part of our project, we explored the effect of micro morphology of monocrystalline silicon surface on primary mouse NSCs’ differentiation. Silicon surface with diverse micro pillars (ranging from 2.5 μm to 20 μm in diameter and space) were used to investigate their effects on NSCs’ differentiation. The results showed that the silicon surface with small diameter and large space micro pillars (e.g., p10-2.5) could effectively enhance the NSCs’ neuron-like cell differentiation. With the decrease of micro pillars’ diameters, the percentage of neuron-like cell differentiation increased. In contrast, the percentage decreased with smaller space between micro pillars. This study might be useful for developing the structural properties of tissue engineering scaffold materials surface.  In the second part of our studies, we detected the sustained release of three kinds of neurotrophic factors, namely NGF, NT-3 and BDNF, encapsulated in the thermosensitive Polyester-Polyether Bearing Pendant Azide / Polypeptide Hydrogel (PLAC). Then we in situ injected the hydrogel mixed with those neurotrophins and neural stem cells into the Ischemia-reperfusion injury area of the rat brain. The effect of the strategy was evaluated by neurological behavior score during 60 days feeding. The mechanism of the therapy was explored from the perspective of inflammation at the same time. As a result, we found that the combination of neural stem cell, hydrogel and neurotrophins could perform a much better therapeutic effect than the other control groups. The order of efficacy for therapy was neural stem cell > neurotrophins and neural stem cell > PLAC. An effective control of the inflammation may be the mechanism it realized its function.

语种: 中文
相关网址: 查看原文
内容类型: 学位论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/125377
Appears in Collections:北京大学深圳医院_学位论文

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作者单位: 北京大学深圳医院

Recommended Citation:
闫东东. 神经干细胞在圆柱体上的分化研究及其联合神经营养因子和聚醚酯/多肽水凝胶在脑卒中治疗方面的探索[D]. 北京大学深圳医院. 北京大学. 2016.
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