Emerging regenerative medicine and tissue engineering strategies for Parkinson's disease.,npj Parkinson's Disease

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Emerging regenerative medicine and tissue engineering strategies for Parkinson's disease.
npj Parkinson's Disease ( IF 6.7 ) Pub Date : 2020-01-08 , DOI: 10.1038/s41531-019-0105-5
James P Harris _{1,

2} , Justin C Burrell _{1,

2,

3} , Laura A Struzyna _{1,

2,

3} , H Isaac Chen _{1,

2} , Mijail D Serruya ₄ , John A Wolf _{1,

2} , John E Duda _{2,

5,

6} , D Kacy Cullen _{1,

2,

3}

Affiliation

Parkinson's disease (PD) is the second most common progressive neurodegenerative disease, affecting 1-2% of people over 65. The classic motor symptoms of PD result from selective degeneration of dopaminergic neurons in the substantia nigra pars compacta (SNpc), resulting in a loss of their long axonal projections to the striatum. Current treatment strategies such as dopamine replacement and deep brain stimulation (DBS) can only minimize the symptoms of nigrostriatal degeneration, not directly replace the lost pathway. Regenerative medicine-based solutions are being aggressively pursued with the goal of restoring dopamine levels in the striatum, with several emerging techniques attempting to reconstruct the entire nigrostriatal pathway-a key goal to recreate feedback pathways to ensure proper dopamine regulation. Although many pharmacological, genetic, and optogenetic treatments are being developed, this article focuses on the evolution of transplant therapies for the treatment of PD, including fetal grafts, cell-based implants, and more recent tissue-engineered constructs. Attention is given to cell/tissue sources, efficacy to date, and future challenges that must be overcome to enable robust translation into clinical use. Emerging regenerative medicine therapies are being developed using neurons derived from autologous stem cells, enabling the construction of patient-specific constructs tailored to their particular extent of degeneration. In the upcoming era of restorative neurosurgery, such constructs may directly replace SNpc neurons, restore axon-based dopaminergic inputs to the striatum, and ameliorate motor deficits. These solutions may provide a transformative and scalable solution to permanently replace lost neuroanatomy and improve the lives of millions of people afflicted by PD.

中文翻译：

帕金森病的新兴再生医学和组织工程策略。

帕金森病 (PD) 是第二常见的进行性神经退行性疾病，影响 65 岁以上人群的 1-2%。PD 的典型运动症状是由黑质致密部 (SNpc) 中的多巴胺能神经元选择性变性引起的，导致失去向纹状体的长轴突投射。目前的治疗策略，如多巴胺替代和深部脑刺激（DBS）只能最大限度地减少黑质纹状体变性的症状，而不能直接替代丢失的通路。人们正在积极寻求基于再生医学的解决方案，其目标是恢复纹状体中的多巴胺水平，几种新兴技术试图重建整个黑质纹状体通路——这是重建反馈通路以确保适当的多巴胺调节的关键目标。尽管许多药理学、遗传学和光遗传学治疗方法正在开发中，但本文重点关注治疗 PD 的移植疗法的演变，包括胎儿移植物、基于细胞的植入物和更新的组织工程结构。重点关注细胞/组织来源、迄今为止的功效以及必须克服的未来挑战，以便能够稳健地转化为临床应用。新兴的再生医学疗法正在使用自体干细胞衍生的神经元进行开发，从而能够构建适合患者特定退化程度的特定结构。在即将到来的恢复性神经外科时代，这种结构可能会直接取代 SNpc 神经元，恢复纹状体基于轴突的多巴胺能输入，并改善运动缺陷。这些解决方案可能提供一种变革性的、可扩展的解决方案，以永久替代丢失的神经解剖结构，并改善数百万帕金森病患者的生活。

更新日期：2020-01-08

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