Human neural stem cells migrate along the nigrostriatal pathway in a primate model of Parkinson's disease
Human neural stem cells migrate along the nigrostriatal pathway in a primate model of Parkinson's disease
复制标题
DOI：
10.1016/j.expneurol.2008.01.025
复制
发表时间：
2008-06-01
影响因子：
5.3
通讯作者：
Sladek, John R., Jr.
中科院分区：
文献类型：
--
作者：
Bjugstad, Kimberly B.;Teng, Yang D.;Sladek, John R., Jr.
尽管损伤定向神经干细胞 (NSC) 迁移的证据在啮齿类动物中已有充分记录，但据我们所知，从未在成年非人类灵长类动物模型中使用人类 NSC (hNSC) 来证实或量化人类神经退行性疾病状态。在本报告中，我们试图提供这一确认，从而有可能将基本干细胞概念推向临床相关性。将 hNSC 植入 7 只成年圣基茨非洲绿猴 (Chlorocebus sabaeus) 的尾状核（双侧）和黑质（单侧），这些猴子之前曾全身接触过 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP)，这是一种破坏多巴胺能黑质纹状体通路的神经毒素。对移植后两个时间点（4 个月和 7 个月）的 hNSC 迁移模式进行了详细的定量分析。沿大脑背腹轴和内侧轴的 hNSC 密度等高线图表明，> 80% 的 hNSC 从植入点迁移到受损的黑质纹状体通路，并沿着受损的黑质纹状体通路迁移。尽管 2/3 的 hNSC 被移植到尾状核内，但在此部位鉴定出 3 x 10(6) 总注射供体细胞的 < 1%。迁移的 hNSC 似乎并不追求神经元谱系。在纹状体和黑质纹状体通路中，但不在黑质中，发现一些 hNSC 具有神经胶质谱系。神经干细胞沿着因特定疾病而功能失调的神经通路进行排列的特性可能是一种有价值的临床工具。 (c) 2008 Elsevier Inc. 保留所有权利。
Although evidence of damage-directed neural stem cell (NSC) migration has been well-documented in the rodent, to our knowledge it has never been confirmed or quantified using human NSC (hNSC) in an adult non-human primate modeling a human neurodegenerative disease state. In this report, we attempt to provide that confirmation, potentially advancing basic stem cell concepts toward clinical relevance. hNSCs were implanted into the caudate nucleus (bilaterally) and substantia nigra (unilaterally) of 7, adult St. Kitts African green monkeys (Chlorocebus sabaeus) with previous exposure to systemic 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), a neurotoxin that disrupts the dopaminergic nigrostriatal pathway. A detailed quantitative analysis of hNSC migration patterns at two time points (4 and 7 months) following transplantation was performed. Density contour mapping of hNSCs along the dorsal-ventral and medial-lateral axes of the brain suggested that > 80% of hNSCs migrated from the point of implantation to and along the impaired nigrostriatal pathway. Although 2/3 of hNSCs were transplanted within the caudate, < 1% of 3 x 10(6) total injected donor cells were identified at this site. The migrating hNSC did not appear to be pursuing a neuronal lineage. In the striatum and nigrostriatal pathway, but not in the substantia nigra, some hNSCs were found to have taken a glial lineage. The property of neural stem cells to align themselves along a neural pathway rendered dysfunctional by a given disease is potentially a valuable clinical tool. (c) 2008 Elsevier Inc. All rights reserved.