Mercado Natosha M, Collier Timothy J, Freeman Thomas, Steece-Collier Kathy
Department of Translational Science & Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA.
Department of Translational Science & Molecular Medicine, College of Human Medicine, Michigan State University, Grand Rapids, MI 49503, USA; Hauenstein Neuroscience Center, Mercy Health Saint Mary's, Grand Rapids, Michigan 49503, USA.
J Clin Cell Immunol. 2016 Dec;7(6). doi: 10.4172/2155-9899.1000476. Epub 2016 Dec 6.
The primary risk factor associated with Parkinson's disease (PD) is advanced age. While there are symptomatic therapies for PD, efficacy of these eventually wane and/or side-effects develop over time. An alternative experimental therapy that has received a great deal of attention over the past several decades has been neural transplantation aimed at replacing nigral dopamine (DA) neurons that degenerate in PD. However, in PD patients and parkinsonian rats, advanced age is associated with inferior benefit following intrastriatal grafting of embryonic DA neurons. Traditionally it has been thought that decreased therapeutic benefit results from the decreased survival of grafted DA neurons and the accompanying poor reinnervation observed in the aged host. However, recent clinical and preclinical data suggest that factors inherent to the aged striatum limit successful brain repair. In this short communication, we focus discussion on the implications of our recent grafting study in aged parkinsonian rats, with additional emphasis on a recent clinical report of the outcome of cell therapy in an aged PD patient with long-term (24 years) survival of DA neuron grafts. To address aging as a limiting factor in successful brain repair, we use the example of cell transplantation as a means to interrogate the environment of the aged striatum and identify factors that may, or may not, respond to interventions aimed at improving the prospects for adequate repair of the aged brain. We offer discussion of how these recent reports, in the context of other historical grafting studies, might provide new insight into specific risk factors that have potential to negatively impact all DA cell or terminal replacement strategies for clinical use in PD.
与帕金森病（PD）相关的主要风险因素是高龄。虽然有针对PD的症状性疗法，但这些疗法的疗效最终会减弱和/或随着时间的推移出现副作用。在过去几十年中受到广泛关注的一种替代性实验疗法是神经移植，旨在替代在PD中退化的黑质多巴胺（DA）神经元。然而，在PD患者和帕金森病大鼠中，高龄与胚胎DA神经元纹状体内移植后获益较差有关。传统上认为，治疗获益降低是由于移植的DA神经元存活率降低以及在老年宿主中观察到的随之而来的再支配不良。然而，最近的临床和临床前数据表明，老年纹状体固有的因素限制了成功的脑修复。在这篇简短的通讯中，我们重点讨论我们最近在老年帕金森病大鼠中进行的移植研究的意义，并特别强调一份关于老年PD患者细胞治疗结果的临床报告，该患者的DA神经元移植长期（24年）存活。为了将衰老作为成功脑修复的限制因素来探讨，我们以细胞移植为例，来审视老年纹状体的环境，并确定可能或可能不会对旨在改善老年脑充分修复前景的干预措施产生反应的因素。我们讨论了在其他既往移植研究的背景下，这些最新报告如何可能为特定风险因素提供新的见解，这些风险因素有可能对所有用于PD临床治疗的DA细胞或终末替代策略产生负面影响。
