Nanotechnology-Based Approaches for Guiding Neural Regeneration.
Nanotechnology-Based Approaches for Guiding Neural Regeneration.
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DOI：
10.1021/acs.accounts.5b00345
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发表时间：
2016-01-19
影响因子：
18.3
通讯作者：
Lee KB
中科院分区：
文献类型：
--
作者：
Shah S;Solanki A;Lee KB
几个世纪以来，哺乳动物的大脑是一种令科学家和临床医生着迷的非凡的“有机机械”。由数百亿个神经元组成的错综复杂的网络，分散在化学和生化成分的混合物中，产生了我们所知道的思想、感觉、记忆和生命。反过来，细微的失衡或对这个系统的破坏可能会导致身体、运动、心理和认知功能的严重并发症。此外，由于中枢神经系统(即大脑和脊髓)的再生能力有限，退行性疾病和创伤造成的不可避免的神经组织损失尤其具有破坏性。在目前的方法中，基于干细胞的再生医学在修复和再生受损的神经组织方面显示出最大的希望。然而，建立受控和可靠的方法来指导干细胞分化为感兴趣的专门神经细胞(例如神经元和少突胶质细胞)一直是该领域的普遍挑战。在这篇文章中，我们总结了我们团队最近开发的基于纳米技术的方法来指导基于干细胞的神经再生。我们的重点是有选择地控制这一过程所采用的三个总体战略。首先，可溶的微环境因素对干细胞的命运起着至关重要的作用。以小分子药物、生化类似物和基于DNA/RNA的载体的形式开发了多种因子来指导神经分化。然而，这些因子的高转染率和最小的细胞毒性一直是具有挑战性的，特别是对干细胞等敏感细胞系。在我们的第一个方法中，我们设计了基于纳米颗粒的系统，以有效地输送这种可溶性因子来控制神经分化。我们的纳米颗粒由有机或无机元素组成，具有生物兼容性，并提供成像和传递等多功能功能。细胞从细胞浸入其中的可溶微环境移动到下面的表面，细胞可以感觉到它们所居住的物理微环境，从而对其做出反应。例如，细胞黏附、形状和铺展的变化是细胞对底层底物表面属性的关键反应。在我们的第二种方法中，我们调节了二维基质的表面化学来控制神经干细胞的形态和由此产生的分化过程。由固定化的细胞外基质(ECM)蛋白和/或纳米材料组成的图案化表面被产生并用于指导神经元的分化和极化。在我们的第三种方法中，在上述方法的基础上，我们通过引入纳米颗粒膜或纳米纤维支架形式的纳米地形特征，进一步调整了细胞−细胞外基质的相互作用。除了提供三维表面形貌外，我们还观察到我们独特的纳米支架可以增强基因传递，促进轴突排列，并选择性地控制分化为感兴趣的神经细胞系。总体而言，基于纳米技术的方法提供了产生适用于神经科学应用的工具所需的精确物理化学控制。
The mammalian brain is a phenomenal piece of “organic machinery” that has fascinated scientists and clinicians for centuries. The intricate network of tens of billions of neurons dispersed in a mixture of chemical and biochemical constituents gives rise to thoughts, feelings, memories, and life as we know it. In turn, subtle imbalances or damage to this system can cause severe complications in physical, motor, psychological, and cognitive function. Moreover, the inevitable loss of nerve tissue caused by degenerative diseases and traumatic injuries is particularly devastating because of the limited regenerative capabilities of the central nervous system (i.e., the brain and spinal cord). Among current approaches, stem-cell-based regenerative medicine has shown the greatest promise toward repairing and regenerating destroyed neural tissue. However, establishing controlled and reliable methodologies to guide stem cell differentiation into specialized neural cells of interest (e.g., neurons and oligodendrocytes) has been a prevailing challenge in the field. In this Account, we summarize the nanotechnology-based approaches our group has recently developed to guide stem-cell-based neural regeneration. We focus on three overarching strategies that were adopted to selectively control this process. First, soluble microenvironmental factors play a critical role in directing the fate of stem cells. Multiple factors have been developed in the form of small-molecule drugs, biochemical analogues, and DNA/RNA-based vectors to direct neural differentiation. However, the delivery of these factors with high transfection efficiency and minimal cytotoxicity has been challenging, especially to sensitive cell lines such as stem cells. In our first approach, we designed nanoparticle-based systems for the efficient delivery of such soluble factors to control neural differentiation. Our nanoparticles, comprising either organic or inorganic elements, were biocompatible and offered multifunctional capabilities such as imaging and delivery. Moving from the soluble microenvironment in which cells are immersed to the underlying surface, cells can sense and consequently respond to the physical microenvironment in which they reside. For instance, changes in cell adhesion, shape, and spreading are key cellular responses to surface properties of the underlying substrate. In our second approach, we modulated the surface chemistry of two-dimensional substrates to control neural stem cell morphology and the resulting differentiation process. Patterned surfaces consisting of immobilized extracellular matrix (ECM) proteins and/or nanomaterials were generated and utilized to guide neuronal differentiation and polarization. In our third approach, building on the above-mentioned approaches, we further tuned the cell−ECM interactions by introducing nanotopographical features in the form of nanoparticle films or nanofiber scaffolds. Besides providing a three-dimensional surface topography, our unique nanoscaffolds were observed to enhance gene delivery, facilitate axonal alignment, and selectively control differentiation into neural cell lines of interest. Overall, nanotechnology-based approaches offer the precise physicochemical control required to generate tools suitable for applications in neuroscience.
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影响因子：
16.6
作者：
Shah, Birju;Yin, Perry T.;Ghoshal, Shraboni;Lee, Ki-Bum
通讯作者：
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影响因子：
64.8
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影响因子：
6.7
作者：
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通讯作者：
Lee KB
影响因子：
29.4
作者：
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Lee, Ki-Bum
石墨烯-纳米颗粒混合结构上神经干细胞的轴突排列和增强的神经元分化。
影响因子：
29.4
作者：
Solanki, Aniruddh;Chueng, Sy-Tsong Dean;Yin, Perry T.;Kappera, Rajesh;Chhowalla, Manish;Lee, Ki-Bum
通讯作者：
Lee, Ki-Bum