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[干细胞:帕金森病移植问题的解决方案?]

[Stem cells: solution to the problem of transplants in Parkinson's disease?].

作者信息

Linazasoro G

机构信息

Centro de Neurologia y Neurocirugia Funcional Clinica Quirón, San Sebstián, España.

出版信息

Neurologia. 2003 Mar;18(2):74-100.

Abstract

The use of neural transplantation or cellular therapies for Parkinson's disease (PD) is based on the idea of substituting nigral dopaminergic neurons lost as a consequence of the degenerative process. More than 400 people with PD have received a transplant with highly variable results. Success of cellular therapy depends on the survival of a sufficient number of trasplanted dopaminergic cells and on the restoration of normal striatal circuitry, disrupted by the disease process. None of the currently used cellular sources can generate an unlimited number of dopaminergic cells. Stem cells (SC) are pluripotent cells which may be obtained from embryonic, fetal or adult tissues. SC can be isolated, expanded in culture during long periods of time and induced to differentiate into dopaminergic cells. Cellular lines can be created and can be stored. Therefore, a large amount of dopaminergic cells can be obtained from a single SC and they can be used when necessary. Embryonic SC seems to be more plastic than adult SC; however, the plasticity of adult SC may be higher than initially thought due to a phenomenon called transdifferentiation. Several studies carried out in experimental models have shown that SC therapy is viable. SC may be also the ideal vehicle for gene therapy. However, much work remains to be done before SC can be applied to human beings. Different aspects of neural development should be elucidated and important practical problems should be overcome, particularly those related to the development of germinal tumors and immunological rejection. Finally, ethical controversies should be carefully managed. Neurología 2003;18(2):74-100

摘要

将神经移植或细胞疗法用于帕金森病(PD)的依据是,用因退行性病变而丧失的黑质多巴胺能神经元进行替代。400多名帕金森病患者接受了移植,但结果差异很大。细胞疗法的成功取决于足够数量的移植多巴胺能细胞的存活以及被疾病过程破坏的正常纹状体回路的恢复。目前使用的任何细胞来源都不能产生无限数量的多巴胺能细胞。干细胞(SC)是多能细胞,可以从胚胎、胎儿或成体组织中获取。干细胞可以分离出来,在培养中长时间扩增,并诱导分化为多巴胺能细胞。可以建立细胞系并储存起来。因此,从单个干细胞可以获得大量多巴胺能细胞,并可在需要时使用。胚胎干细胞似乎比成体干细胞更具可塑性;然而,由于一种称为转分化的现象,成体干细胞的可塑性可能比最初认为的要高。在实验模型中进行的几项研究表明,干细胞疗法是可行的。干细胞也可能是基因治疗的理想载体。然而,在将干细胞应用于人类之前,仍有许多工作要做。神经发育的不同方面需要阐明,重要的实际问题需要克服,特别是与生殖细胞瘤的发生和免疫排斥相关的问题。最后,伦理争议需要谨慎处理。《神经学》2003年;18(2):74 - 100

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