Transplantation of human amniotic cells exerts neuroprotection in MPTP-induced Parkinson disease mice

Transplantation of human amniotic cells exerts neuroprotection in MPTP-induced Parkinson disease mice
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DOI:
10.1016/j.brainres.2008.02.040
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发表时间:
2008-04-18
期刊:
影响因子:
2.9
通讯作者:
Zuo, Ping-Ping
Zuo, Ping-Ping
中科院分区:
医学3区
文献类型:
--
作者:
Kong, Xiang-Ying;Cai, Zhe;Zuo, Ping-Ping

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目的 确定培养的人羊膜细胞 (HAC) 移植到 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 诱导的帕金森病 (PD) 小鼠脑中后的存活和分化。通过注射MPTP(15 mg/kg,第四次,间隔2 h)建立PD小鼠模型。从人体内分离的HACs经过PKH26标记后,被移植到PD小鼠的纹状体中。采用免疫组织化学方法评价MPTP在体内的毒性。黑质,移植物存活和内源性神经发生。通过 ELISA 检测纹状体中脑源性神经营养因子 (BDNF) 和胶质细胞源性神经营养因子 (GDNF) 的水平。我们的结果表明,培养的HACs可以表达神经祖细胞的标志物并分化为神经元、多巴胺能神经元、星形胶质细胞和少突胶质细胞。质内TH阳性神经细胞明显减少。模型小鼠的黑质含量增加,而移植小鼠的黑质含量增加。免疫组织学结果显示,移植的HACs在PD模型小鼠的大脑中存活并迁移,但没有观察到形态整合。移植小鼠脑室下区 (SVZ) 的 BrdU 阳性细胞和纹状体的神经营养素增加。结果表明,移植的HACs能够存活并促进小鼠内源性神经发生,这可能与纹状体神经营养蛋白水平增加有关。 (C) 2008 Elsevier B.V. 保留所有权利。
To determine the survival and differentiation of cultured Human amniotic cells (HACs) upon transplantation into the brain of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)induced Parkinson disease (PD) mice. Mouse model of PD was established with injections of MPTP (15 mg/kg, fourth, 2 h interval). After being labeled with PKH26, HACs isolated from human were transplanted into the striatum of PD mice. Immunohistochemistry was performed to evaluate the toxicity of MPTP in the substantia. nigra, graft survival and endogenous neurogenesis. Brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) level in the striatum were tested by ELISA. Our results showed that cultured HACs can express the marker of neural progenitor cells and differentiate into neuron, dopaminergic neuron, astrocyte and oligodendrocyte. TH-positive neural cells were significantly reduced in the substantia. nigra in the model mice, whereas which increased in transplantation mice. Immunohistology results showed that transplanted HACs survived and migrated in the brain of PD model mouse, though no morphological integration was observed. BrdU-positive cells in the Subventricular zone (SVZ) and neurotrophins of the striatum increased in the transplantation mice. The results suggested that transplanted HACs could survive and promote the endogenous neurogenesis of mice, which maybe related to the increased level of neurotrophins of the striatum. (C) 2008 Elsevier B.V. All rights reserved.