中国神经再生研究(英文版) ›› 2017, Vol. 12 ›› Issue (3): 389-392.doi: 10.4103/1673-5374.202935

• 综述:退行性病与再生 • 上一篇    下一篇

帕金森病的神经嫁接:挑战与展望

  

  • 收稿日期:2017-03-06 出版日期:2017-03-15 发布日期:2017-03-15
  • 基金资助:

    本文赞助机构包括:医学研究委员会,惠康信托干细胞研究所(剑桥),NIHR剑桥生物医学研究中心,生物技术与生物科学研究理事会和英国工程和自然科学研究委员会。

Neural grafting for Parkinson’s disease: challenges and prospects

Thomas B. Stoker1, 2, Nicholas F. Blair1, 2, Roger A. Barker1, 2   

  1. 1 John van Geest Center for Brain Repair, Department of Clinical Neurosciences, University of Cambridge, Cambridge, UK; 2 Wellcome Trust – Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK
  • Received:2017-03-06 Online:2017-03-15 Published:2017-03-15
  • Contact: Thomas B. Stoker, BA (Hons)MB BChir, tbs26@cam.ac.uk.
  • Supported by:

    The authors acknowledge financial support from the following organizations: Medical Research Council, Wellcome Trust Stem Cell Institute (Cambridge), NIHR Cambridge Biomedical Research Center, the Biotechnology and Biological Sciences Research Council and the Engineering and Physical Sciences Research Council. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in this manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents, received or pending, or royalties. No writing assistance was utilized in the production of this manuscript.

摘要:

帕金森病(PD)是一种神经退行性病症,临床表现为由运动迟缓,僵硬和休息性震颤组成的运动障碍,主要原因在于纹状体多巴胺消耗的黑质多巴胺能神经元退化。此外,其他区域的病理变化会导致痴呆,神经精神表现包括抑郁和焦虑,睡眠障碍,包括快速眼动睡眠行为障碍和自主神经功能。PD的运动障碍对多巴胺替代疗法(例如左旋多巴或多巴胺激动剂)反应良好。然而,多巴胺能药物的全身给药导致纹状体中多巴胺的非生理释放,导致有时使运动性运动障碍和脱靶效应失效,导致神经精神并发症,包括冲动控制行为。因此,目前对以更加生理和靶向方式将多巴胺引入纹状体的手段需要尚未满足,因此研究者们对于PD的新兴的基于细胞的再生治疗有很多兴趣,并且已经研究了多种多巴胺能细胞来源用于治疗PD,本文讨论了这些来源的基础,以及它们在临床实践中的应用前景。

ORCID:0000-0001-5186-7630(Thomas B. Stoker)

Abstract:

Parkinson’s disease (PD) is a neurodegenerative condition which causes a characteristic movement disorder secondary to loss of dopaminergic neurons in the substanitia nigra. The motor disorder responds well to dopamine-replacement therapies, though these result in significant adverse effects due to non-physiological release of dopamine in the striatum, and off-target effects. Cell-based regenerative treatments offer a potential means for targeted replacement of dopamine, in a physiological manner. Dopaminergic neurons for cell-based therapies can be obtained from several sources. Fetal ventral mesencephalon tissue contains dopaminergic neuron progenitors, and has been transplanted into the striatum of PD patients with good results in a number of cases. However, the ethical implications and logistical challenges of using fetal tissue mean that fetal ventral mesencephalon is unlikely to be used in a widespread clinical setting. Induced pluripotent stem cells can be used to generate dopaminergic neurons for transplantation, providing a source of autologous tissue for grafting. This approach means that challenges associated with allografts, such as the potential for immune rejection, can be circumvented. However, the associated cost and difficulty in producing a standardized product from different cell lines means that, at present, this approach is not commercially
viable as a cell-based therapy. Dopaminergic neurons derived from embryonic stem cells offer the most promising basis for a cell-based therapy for Parkinson’s disease, with trials due to commence in the next few years. Though there are ethical considerations to take into account when using embryonic tissue, the possibility of producing a standardized, optimized cell product means that this approach can be both effective, and commercially viable.

Key words: Parkinson’s disease, neural grafting, embryonic stem cells, induced pluripotent stem cells, induced neurons, cell-based therapies