Cells therapy for Parkinson's disease--so close and so far away.

ZhenHua Ren, Yu Zhang
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引用次数: 15

Abstract

One of the strategies of treating Parkinson's disease (PD) is the replacement of lost neurons in the substantia nigra with healthy dapamingergic cells. Potential sources for cells range from autologous grafts of dopamine secreting cells, fetal ventral mesencephalon tissue, to various stem cell types. Over the past quarter century, many experimental replacement therapies have been tried on PD animal models as well as human patients, yet none resulted in satisfactory outcomes that warrant wide applications. Recent progress in stem cell biology has shown that nuclear transfer embryonic stem cells (ntES) or induced pluripotent stem cells (iPS) derived cells can be used to successfully treat rodent PD models, thus solving the problem of immunorejection and paving the way for future autologous transplantations for treating PD. Meanwhile, however, post mortem analysis of patients who received fetal brain cell transplantation revealed that implanted cells are prone to degeneration just like endogenous neurons in the same pathological area, indicating long-term efficacy of cell therapy of PD needs to overcome the degenerating environment in the brain. A better understanding of neurodegeneration in the midbrain appeared to be a necessary step in developing new cell therapies in Parkinson's disease. It is likely that future cell replacement will focus on not only ameliorating symptoms of the disease but also trying to slow the progression of the disease by either neuroprotection or restoring the micro-environment in the midbrain.

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帕金森氏症的细胞疗法——如此近又如此远。
治疗帕金森病(PD)的策略之一是用健康的达胺能细胞替代黑质中丢失的神经元。细胞的潜在来源包括多巴胺分泌细胞、胎儿腹侧中脑组织的自体移植物,以及各种干细胞类型。在过去的四分之一世纪里,许多实验替代疗法已经在PD动物模型和人类患者身上进行了试验,但没有一种结果令人满意,值得广泛应用。干细胞生物学的最新进展表明,核移植胚胎干细胞(ntES)或诱导多能干细胞(iPS)衍生细胞可成功用于治疗啮齿动物帕金森病模型,从而解决免疫排斥问题,为未来自体移植治疗帕金森病铺平道路。但同时,对接受胎儿脑细胞移植患者的尸检分析显示,植入的细胞与同一病理区域内的内源性神经元一样,也容易发生变性,说明PD细胞治疗的长期疗效需要克服大脑内的变性环境。更好地了解中脑神经退行性变似乎是开发帕金森病新细胞疗法的必要步骤。很可能未来的细胞替换将不仅集中于改善疾病的症状,而且还将试图通过神经保护或恢复中脑的微环境来减缓疾病的进展。
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