Cell therapy for Parkinson's disease is coming of age: current challenges and future prospects with a focus on immunomodulation.,Gene Therapy

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Cell therapy for Parkinson's disease is coming of age: current challenges and future prospects with a focus on immunomodulation.
Gene Therapy ( IF 4.6 ) Pub Date : 2019-04-16 , DOI: 10.1038/s41434-019-0077-4
Shirley D Wenker ₁ , Fernando J Pitossi ₁

Affiliation

Parkinson's disease (PD) is a neurodegenerative disease that affects more than 1% of people over the age of 60. The principal feature of this disease is the progressive loss of dopaminergic neurons (DAn) within the nigrostriatal system, causing the motor symptoms observed in these patients. At present, there is no therapeutic approach with a cytoprotective effect that can prevent DAn cell death or disease progression. Cell replacement therapy began 30 years ago with the objective to compensate for the loss of DAn by transplantation of dopamine-producing cells. The results from these trials have provided proof of concept of safety and efficacy of cell replacement. However, a major limiting factor of this strategy has been the poor survival rate of grafted DAn. An important factor that could cause cell death of DA precursors is the host response to the graft. In this review, we discuss the factors that affect the outcome of cell therapy in PD, with focus on the cell types used and the functional effects of the host immune response on graft survival and differentiation. We also discuss the strategies that may increase the efficacy of cell replacement therapy which target the host immune response.

中文翻译：

帕金森病的细胞疗法正在走向成熟：当前的挑战和未来的前景，重点是免疫调节。

帕金森病 (PD) 是一种神经退行性疾病，影响超过 1% 的 60 岁以上人群。这种疾病的主要特征是黑质纹状体系统内的多巴胺能神经元 (DAn) 进行性丧失，导致在这些病人。目前，没有具有细胞保护作用的治疗方法可以防止DAn细胞死亡或疾病进展。细胞替代疗法始于 30 年前，其目的是通过移植产生多巴胺的细胞来补偿 DAn 的损失。这些试验的结果证明了细胞替代的安全性和有效性概念。然而，该策略的一个主要限制因素是移植的 DAn 的存活率低。可能导致 DA 前体细胞死亡的一个重要因素是宿主对移植物的反应。在这篇综述中，我们讨论了影响 PD 细胞治疗结果的因素，重点关注所使用的细胞类型以及宿主免疫反应对移植物存活和分化的功能影响。我们还讨论了可能提高针对宿主免疫反应的细胞替代疗法疗效的策略。

更新日期：2019-11-18

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