帕金森病是最常见的神经退行性疾病之一，60岁以上人群相对高发。它起源于黑质中多巴胺能神经元的退化，患者身体的运动机能受损，出现颤抖和行走困难。近日，研究人员发明了一种纳米结构，可以刺激神经干细胞分化成神经细胞，移植到患有帕金森的大鼠体内后逐渐改善了疾病症状。相关研究结果发表在Advanced Science上。研究人员首先诱导特定神经干细胞分化成微型黑质样结构（miniature SN-like structures，mini-SNLSs)。这些mini-SNLSs主要由多巴胺能神经元组成，可替代脑内黑质受损或退化的细胞。纳米矩阵由涂有纳米结构层的二氧化硅板组成，表面有数万亿个纳米之字形结构，可以在不使用化学生长因子的情况下启动神经干细胞向mini-SNLSs生长。当神经干细胞在体外与定制的纳米之字形基质进行物理接触时，可以诱导细胞迅速分化为所需的多巴胺能神经元。研究人员将纳米之字形基质培养的mini-SNLSs移植到帕金森病大鼠的大脑中。移植后第8周开始，所有大鼠的旋转功能均有改善；在第18周，观察到多巴胺能神经元广泛分布于移植的原发部位。此外，研究中未发现肿瘤样特征，提示致癌的风险低。这些结果表明，通过诱导神经干细胞生长分化形成微型脑样结构在大鼠大脑中表现出良好的生存能力和功能，对帕金森病大鼠有进展性改善作用，为干细胞疗法治疗帕金森病提供了新的理论支持。
推荐阅读原文：
Extracellular Nanomatrix-Induced Self-Organization of Neural Stem Cells into Miniature Substantia Nigra-Like Structures with Therapeutic Effects on Parkinsonian Rats.
Substantia nigra (SN) is a complex and critical region of the brain wherein Parkinson"s disease (PD) arises from the degeneration of dopaminergic neurons. Miniature SN-like structures (mini-SNLSs) constructed from novel combination of nanomaterials and cell technologies exhibit promise as potentially curative cell therapies for PD. In this work, a rapid self-organization of mini-SNLS, with an organizational structure and neuronal identities similar to those of the SN in vivo, is achieved by differentiating neural stem cells in vitro on biocompatible silica nanozigzags (NZs) sculptured by glancing angle deposition, without traditional chemical growth factors. The differentiated neurons exhibit electrophysiological activity in vitro. Diverse physical cues and signaling pathways that are determined by the nanomatrices and lead to the self-organization of the mini-SNLSs are clarified and elucidated. In vivo, transplantation of the neurons from a mini-SNLS results in an early and progressive amelioration of PD in rats. The sculptured medical device reported here enables the rapid and specific self-organization of region-specific and functional brain-like structures without an undesirable prognosis. This development provides promising and significant insights into the screening of potentially curative drugs and cell therapies for PD.
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