PET imaging of implanted human retinal pigment epithelial cells in the MPTP-induced primate model of Parkinson's disease
PET imaging of implanted human retinal pigment epithelial cells in the MPTP-induced primate model of Parkinson's disease
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DOI：
10.1016/j.expneurol.2004.06.009
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发表时间：
2004-10-01
影响因子：
5.3
通讯作者：
Allen, RC
中科院分区：
文献类型：
--
作者：
Doudet, DJ;Cornfeldt, ML;Allen, RC
人视网膜色素上皮(HRPE)细胞产生L多巴，易于在培养中获得和扩增，并附着在微载体上，可以在没有免疫抑制的情况下在脑内存活。在大鼠、灵长类动物和帕金森患者中的研究表明，纹状植入的hRPE细胞附着到明胶微载体(RPE-GM)能够改善帕金森症状，并具有良好的长期耐受性。在双侧1-甲基-4-苯基-1，2，3，6-四氢吡啶盐酸盐(MPTP)诱导的帕金森综合征中，中度到严重损害的猴子接受了壳核内单侧RPE-GM植入，在植入后的前2个月中，临床评分改善了39%。正电子发射断层扫描显示植入的壳核中的[F-18]-L-多巴蓄积增加，与对侧壳核相比，[C-11]雷氯普利的结合减少，提示多巴胺的释放增加。我们首次报道了hRPE细胞及其作用的体内可视化，暗示了多巴胺能作用机制。(C)2004 Elsevier Inc.保留所有权利。
Human retinal pigment epithelial (hRPE) cells produce L-dopa, are easily harvested and expanded in culture, and, attached to microcarriers, can survive in the brain without immunosuppression. Studies in rats, primates, and parkinsonian patients have demonstrated that striatally implanted hRPE cells attached to gelatin microcarriers (RPE-GM) are able to improve parkinsonian symptoms and are well tolerated for extended periods. In moderately to severely impaired monkeys with bilateral 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine hydrochloride (MPTP)-induced parkinsonism receiving a unilateral RPE-GM implant in the putamen, there was a 39% improvement in clinical scores over the first 2 months post-implant. Positron emission tomography (PET) with [F-18]fluoro-L-dopa (FDOPA) showed increased accumulation in the implanted putamen and a concomitant decrease in [C-11]raclopride binding in the same area, suggesting increased dopamine release compared to the contralateral putamen. We report the first in vivo visualization of hRPE cells and their effects, implicating a dopaminergic mechanism of action. (C) 2004 Elsevier Inc. All rights reserved.