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干细胞作为神经退行性疾病的一种潜在治疗方法。

The stem cells as a potential treatment for neurodegeneration.

作者信息

Daniela Ferrari, Vescovi Angelo Luigi, Bottai Daniele

机构信息

Stem Cell Research Institute, DIBIT Fondazione Centro San Raffaele del Monte Tabor, Milan, Italy.

出版信息

Methods Mol Biol. 2007;399:199-213. doi: 10.1007/978-1-59745-504-6_14.

Abstract

Cell degeneration and death, be it extensive and widespread, such as in metabolic disorders, or focal and selective as in Parkinson's disease (PD), is the underlying feature of many neurological diseases. Thus, the replacement of cells lost by injury or disease has become a central tenet in strategies aiming at the development of novel therapeutic approaches for neurodegenerative disorders. In addition to the in vivo recruitment of endogenous cells, which is now emerging as a promising novel strategy, the transplantation of new, exogenously generated brain cells is probably the most extensively studied methodology for cell replacement in the central nervous system, with the initial experimental clinical studies in PD dating back to the early 1970s (Bjorklund, A. and Stenevi, U., 1984, Intracerebral neural implants: neuronal replacement and reconstruction of damaged circuitries. Annu Rev Neurosci 7, 279-308; Snyder, B. J. and Olanow, C. W., 2005, Stem cell treatment for Parkinson's disease: an update for 2005. Curr Opin Neurol 18, 376-85). The need to generate the cells to be transplanted in large quantities and in a reproducible, steady, and safe fashion has long represented one of the major issues in this field, regardless of whether one was trying to produce specific cell subtypes or uncommitted and highly plastic neural precursors, which would respond to local, instructive cues, upon transplantation into the damaged area. Neural stem cells (NSCs), with their capacity for long-term expansion in vitro and their extensive functional stability and plasticity, allow now for the establishment of cultures of mature neural cells as well as highly undifferentiated precursors and are emerging as one of the most amenable cell sources for neural transplantation (Gage, F. H., 2000, Mammalian neural stem cells. Science 287, 1433-8; McKay, R., 1997, Stem cells in the central nervous system. Science 276, 66-71). This chapter illustrates the basic aspect of the handling and preparation of NSCs for experimental transplantation in two animal models of neurodegenerative disorders, namely, postcontusion spinal cord injury and multiple sclerosis.

摘要

细胞变性和死亡,无论是广泛而普遍的,如在代谢紊乱中,还是局部性和选择性的,如在帕金森病(PD)中,都是许多神经疾病的基本特征。因此,替代因损伤或疾病而丢失的细胞已成为旨在开发神经退行性疾病新治疗方法的策略中的核心原则。除了体内募集内源性细胞(这一方法正作为一种有前景的新策略崭露头角)之外,移植新的、外源性生成的脑细胞可能是中枢神经系统中用于细胞替代研究最为广泛的方法,针对PD的初步实验性临床研究可追溯到20世纪70年代早期(比约克隆德,A.和斯特内维,U.,1984年,《脑内神经植入物:神经元替代与受损神经回路的重建》。《神经科学年度评论》7卷,279 - 308页;斯奈德,B. J.和奥洛诺,C. W.,2005年,《帕金森病的干细胞治疗:2005年最新进展》。《当代神经病学观点》18卷,376 - 385页)。长期以来,无论人们试图生成特定的细胞亚型还是未分化且具有高度可塑性的神经前体细胞(这些细胞在移植到受损区域后会对局部的诱导信号作出反应),以大量且可重复、稳定和安全的方式生成待移植细胞的需求一直是该领域的主要问题之一。神经干细胞(NSCs)具有在体外长期扩增的能力以及广泛的功能稳定性和可塑性,现在能够建立成熟神经细胞以及高度未分化前体细胞的培养物,并且正成为神经移植中最适宜的细胞来源之一(盖奇,F. H.,2000年,《哺乳动物神经干细胞》。《科学》287卷,1433 - 1438页;麦凯,R.,1997年,《中枢神经系统中的干细胞》。《科学》276卷,66 - 71页)。本章阐述了在两种神经退行性疾病动物模型(即挫伤性脊髓损伤和多发性硬化症)中,为实验性移植处理和制备神经干细胞的基本方面。

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