Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease
Cell type analysis of functional fetal dopamine cell suspension transplants in the striatum and substantia nigra of patients with Parkinson's disease
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DOI：
10.1093/brain/awh510
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发表时间：
2005-07-01
期刊：
影响因子：
14.5
通讯作者：
Isacson, O
中科院分区：
文献类型：
--
作者：
Mendez, I;Sanchez-Pernaute, R;Isacson, O
我们首次报告了两名帕金森氏病患者的尸检分析，他们接受了胎儿中脑移植作为纹状体细胞悬浮液，在一例中还接受了黑质细胞移植。这些患者的临床进展良好，F-18-氟多巴正电子发射计算机断层扫描阳性，没有出现运动并发症。移植后存活的多巴胺神经元与正常对照组黑质(n=3)的酪氨酸羟化酶、G蛋白偶联内向整流钾通道2型(Girk2)和钙结合蛋白等表型标志物呈阳性反应。移植物恢复了帕金森病患者大脑中受影响最严重的纹状体区域提供特定多巴胺能神经支配的细胞类型。这样的移植能够用新的多巴胺纤维密集地重新支配宿主壳核。这些患者只接受了6个月的标准免疫抑制，但通过对小胶质细胞CD45和CD68标记的分析，术后3-4年的尸检分析显示，移植对宿主大脑的免疫原性只是轻微的。这项研究表明，使用这些方法，多巴胺神经元替代细胞疗法对晚期疾病患者可能是有益的，改变技术方法可能会对神经移植后的疗效和不良事件产生有利影响。
We report the first post-mortem analysis of two patients with Parkinson's disease who received fetal midbrain transplants as a cell suspension in the striatum, and in one case also in the substantia nigra. These patients had a favourable clinical evolution and positive F-18-fluorodopa PET scans and did not develop motor complications. The surviving transplanted dopamine neurons were positively identified with phenotypic markers of normal control human substantia nigra (n = 3), such as tyrosine hydroxylase, G-protein-coupled inward rectifying current potassium channel type 2 (Girk2) and calbindin. The grafts restored the cell type that provides specific dopaminergic innervation to the most affected striatal regions in the parkinsonian brain. Such transplants were able to densely reinnervate the host putamen with new dopamine fibres. The patients received only 6 months of standard immune suppression, yet by post-mortem analysis 3-4 years after surgery the transplants appeared only mildly immunogenic to the host brain, by analysis of microglial CD45 and CD68 markers. This study demonstrates that, using these methods, dopamine neuronal replacement cell therapy can be beneficial for patients with advanced disease, and that changing technical approaches could have a favourable impact on efficacy and adverse events following neural transplantation.