Human Fetal Neural Stem Cells for Neurodegenerative Disease Treatment
Human Fetal Neural Stem Cells for Neurodegenerative Disease Treatment
复制标题
DOI：
10.1007/978-3-319-93485-3_14
复制
发表时间：
2018-01-01
期刊：
影响因子：
--
通讯作者：
Vescovi, Angelo Luigi
中科院分区：
文献类型：
--
作者：
Ferrari, Daniela;Gelati, Maurizio;Vescovi, Angelo Luigi
帕金森氏症的临床试验，使用初级大脑胎儿组织，已经证明神经干细胞治疗可能适用于神经退行性疾病。胎儿组织的使用提出了几个问题，阻碍了这种方法的临床发展。除了需要持续供应胎儿标本的伦理问题外，在一次移植中使用来自多个胎儿的细胞的必要性大大加剧了这个问题。不同供体的细胞活力和组成各不相同，此外，供体细胞的异质性增加了免疫排斥或污染的可能性。细胞治疗的理想细胞来源是可再生的，从而消除了对原代胎儿组织移植的需要，并且还允许生存能力、不育性、细胞组成和细胞成熟得到控制，同时本身不致瘤。能够将胎儿组织的可塑性与广泛的增殖能力和功能稳定性结合起来的连续和标准化的临床级正常人类神经细胞的可用性，对于中枢神经系统（CNS）疾病的细胞治疗转化为临床至关重要。在这里，我们描述了一个完善的方案，以生产人类神经干细胞遵循GMP指南，使我们能够获得“临床级”细胞系。
Clinical trials for Parkinson's disease, which used primary brain fetal tissue, have demonstrated that neural stem cell therapy could be suitable for neuro-degenerative diseases. The use of fetal tissue presents several issues that have hampered the clinical development of this approach. In addition to the ethical concerns related to the required continuous supply of fetal specimen, the necessity to use cells from multiple fetuses in a single graft greatly compounded the problem. Cell viability and composition vary in different donors, and, further, the heterogeneity in the donor cells increased the probability of immunological rejection or contamination. An ideal cell source for cell therapy is one that is renewable, thus eliminating the need for transplantation of primary fetal tissue, and that also allows for viability, sterility, cell composition, and cell maturation to be controlled, while being inherently not tumorigenic. The availability of continuous and standardized clinical grade normal human neural cells, able to combine the plasticity of fetal tissue with an extensive proliferating capacity and functional stability, would be of paramount importance for the translation of cell therapy for central nervous system (CNS) disorders into the clinic. Here we describe a well-established protocol to produce human neural stem cells following GMP guidelines that allows us to obtain "clinical grade" cell lines.