Towards stem cell replacement therapies for Parkinson's disease
Towards stem cell replacement therapies for Parkinson's disease
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DOI：
10.1016/j.bbrc.2010.04.037
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发表时间：
2010-05-21
影响因子：
3.1
通讯作者：
Arenas, Ernest
中科院分区：
文献类型：
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作者：
Arenas, Ernest
目前帕金森氏病(PD)的治疗方法提供了症状缓解，但没有一种方法改变了病程。因此，显然需要再生和细胞替代疗法(CRT)。然而，CRT面临着几个重要的挑战。首先，帕金森病的主要症状是中脑多巴胺(DA)神经元的丧失，但其他类型的细胞也会受到影响。其次，移植流产胎儿的腹侧中脑组织已经导致了CRT可能起作用的原理证明，然而，它也指出了与患者、手术和细胞准备相关的重要变量，这些变量需要改进。第三，虽然一些患者出现了运动障碍，随着时间的推移，移植细胞中出现了路易小体，但另一些患者的病情有了显著改善，能够停止服药。今天有没有PD CRT的案例？干细胞对CRT的可能贡献是什么？在这篇综述中，我将讨论我们从使用胎儿组织移植的临床试验中学到了什么，为CRT开发人类干细胞衍生的DA神经元的最新进展，以及为了将干细胞发展为PD CRT的工具需要解决的一些问题。(C)2010 Elsevier Inc.保留所有权利。
Current therapeutic approaches for Parkinson's disease (PD) provide symptomatic relief but none of them change the course of disease. There is therefore a clear need for regenerative and cell replacement therapies (CRT). However, CRT faces several important challenges. First, the main symptoms of PD result from the loss of midbrain dopamine (DA) neurons, but other cell types are also affected. Second, transplantation of human ventral midbrain tissue from aborted fetuses has lead to proof of principle that CRT may work, however, it has also pointed out to important patient-, surgery- and cell preparation-related variables, which need to be improved. Third, while some patients have developed dyskinesias and, with time, Lewy bodies in the grafted cells, other patients have experienced remarkable improvement and have been able to stop their medication. Is there a case for PD CRT today? What is the possible contribution of stem cells to CRT? In this review, I will discuss what we learned from clinical trials using fetal tissue grafts, recent progress in the development of human stem cell-derived-DA neurons for CRT, and some of the issues that need to be solved in order to develop stem cells as tools for PD CRT. (C) 2010 Elsevier Inc. All rights reserved.