Cell therapy for Parkinson's disease: Why it doesn't work every time
Cell therapy for Parkinson's disease: Why it doesn't work every time
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DOI：
10.1002/mds.27742
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发表时间：
2019-08-01
影响因子：
8.6
通讯作者：
Steece-Collier, Kathy
中科院分区：
文献类型：
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作者：
Collier, Timothy J.;Sortwell, Caryl E.;Steece-Collier, Kathy
细胞替代疗法治疗晚期PD的临床经验取得了显著的成功和失败。最近的一份尸检病例报告显示，一名16年前接受胎儿多巴胺神经元植入的个体，尽管移植神经元存活率最高，纹状体神经再支配最广泛，但从未经历过临床获益，这引发了令人清醒的问题。有充分的理由，细胞替代科学的大量努力继续集中在优化细胞来源和植入程序上。在这里，我们描述了我们在老年大鼠的临床前研究表明，尽管存活的大量移植多巴胺神经元和密集的纹状体神经再支配，移植物和宿主之间的突触连接显着减少和行为恢复受损。这使我们的假设，多巴胺神经元移植的治疗反应的变化可能是少的移植神经元的活力和更多的关于老年人的完整性，多巴胺耗尽纹状体及其修复能力。只有在正确的靶点存在的情况下，多巴胺神经支配的替代才能完全有效。(c)2019年，任作家。出版社：Wiley Periodicals，Inc.国际帕金森和运动障碍协会（International Parkinson and Movement Disorder Society）
The clinical experience with cell replacement therapy for advanced PD has yielded notable successes and failures. A recent autopsy case report of an individual that received implants of fetal dopamine neurons 16 years previously, but at no time experienced clinical benefit despite the best documented survival of grafted neurons and most extensive reinnervation of the striatum, raises sobering issues. With good reason, a great deal of effort in cell replacement science continues to focus on optimizing the cell source and implantation procedure. Here, we describe our preclinical studies in aged rats indicating that despite survival of large numbers of transplanted dopamine neurons and dense reinnervation of the striatum, synaptic connections between graft and host are markedly decreased and behavioral recovery is impaired. This leads us to the hypothesis that the variability in therapeutic response to dopamine neuron grafts may be less about the viability of transplanted neurons and more about the integrity of the aged, dopamine-depleted striatum and its capacity for repair. Replacement of dopamine innervation only can be fully effective if the correct target is present. (c) 2019 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.