Grafted Miniature-Swine Neural Stem Cells of Early Embryonic Mesencephalic Neuroepithelial Origin can Repair the Damaged Neural Circuitry of Parkinson's Disease Model Rats.
Grafted Miniature-Swine Neural Stem Cells of Early Embryonic Mesencephalic Neuroepithelial Origin can Repair the Damaged Neural Circuitry of Parkinson's Disease Model Rats.
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移植的早期胚胎中脑神经上皮来源的小型猪神经干细胞可以修复帕金森病模型大鼠受损的神经回路。
DOI：
10.1016/j.neuroscience.2018.06.007
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发表时间：
2018
期刊：
影响因子：
3.3
通讯作者：
Hayashi T & Kawase T.
中科院分区：
文献类型：
--
作者：
Mine Y;Momiyama T;Hayashi T & Kawase T.
虽然近年来在利用人iPS细胞来源的中脑多巴胺能祖细胞方面取得了显著进展，但在基底神经节相关疾病的治疗策略中，替代物是必不可少的，神经干细胞（neural stem cells，NSCs）由于其多能性和自我更新的特性而成为神经移植的可能供体材料之一。本研究将胚胎17和18天的小型猪中脑神经上皮干细胞（M-NESC）移植到帕金森病大鼠纹状体内，对其进行生物化学、行为学和电生理学评价，以证实其作为神经异种移植供体材料的可行性。移植的小型猪M-NESC在帕金森病大鼠纹状体中存活8周后，其中许多分化为酪氨酸羟化酶（TH）阳性细胞。移植小型猪M-NESC的帕金森病模型大鼠表现出帕金森病行为缺陷的功能恢复。大多数供体来源的TH阳性细胞在8周时表现出成熟的形态。在移植的宿主大鼠脑切片中，供体来源的神经元的全细胞记录显示存在多种类型的神经元，包括多巴胺能神经元。刺激宿主区可诱发谷氨酸能和GABA能突触后电流，提示它们同时接受来自宿主区的兴奋性和抑制性突触输入。目前的研究表明，非啮齿类哺乳动物M-NESC可以分化为功能活跃的神经元在疾病异种环境中，并可以改善帕金森氏症的行为缺陷的物种。神经上皮干细胞可能是一个有吸引力的候选人作为供体材料的来源，神经移植。
Although recent progress in the use of human iPS cell-derived midbrain dopaminergic progenitors is remarkable, alternatives are essential in the strategies of treatment of basal-ganglia-related diseases.Attention has been focused on neural stem cells (NSCs) as one of the possible candidates of donor material for neural transplantation, because of their multipotency and self-renewal characteristics. In the present study, miniature-swine (mini-swine) mesencephalic neuroepithelial stem cells (M-NESCs) of embryonic 17 and 18 days grafted in the parkinsonian rat striatum were assessed immunohistochemically, behaviorally and electrophysiologically to confirm their feasibility for the neural xenografting as a donor material. Grafted mini-swine M-NESCs survived in parkinsonian rat striatum at 8 weeks after transplantation and many of them differentiated into tyrosine hydroxylase (TH)-positive cells. The parkinsonian model rats grafted with mini-swine M-NESCs exhibited a functional recovery from their parkinsonian behavioral defects. The majority of donor-derived TH-positive cells exhibited a matured morphology at 8 weeks. Whole-cell recordings from donor-derived neurons in the host rat brain slices incorporating the graft revealed the presence of multiple types of neurons including dopaminergic. Glutamatergic and GABAergic post-synaptic currents were evoked in the donor-derived cells by stimulation of the host site, suggesting they receive both excitatory and inhibitory synaptic inputs from host area. The present study shows that non-rodent mammalian M-NESCs can differentiate into functionally active neurons in the diseased xenogeneic environment and could improve the parkinsonian behavioral defects over the species. Neuroepithelial stem cells could be an attractive candidate as a source of donor material for neural transplantation.