Endometrial stem cell transplantation restores dopamine production in a Parkinson's disease model.
Endometrial stem cell transplantation restores dopamine production in a Parkinson's disease model.
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DOI：
10.1111/j.1582-4934.2010.01068.x
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发表时间：
2011-04
影响因子：
5.3
通讯作者：
Taylor HS
中科院分区：
文献类型：
--
作者：
Wolff EF;Gao XB;Yao KV;Andrews ZB;Du H;Elsworth JD;Taylor HS
帕金森病（Parkinson's disease，PD）是一种由多巴胺能神经元丢失引起的神经退行性疾病。成人子宫内膜衍生干细胞（HEDSC），一种容易获得的间充质干细胞样细胞，用于产生多巴胺能细胞和用于移植。表达CD 90、血小板衍生生长因子（PDGF）-Rβ和CD 146但不表达CD 45或CD 31的细胞在体外分化为多巴胺能神经元，这些神经元表现出轴突投射、锥体细胞体和树突状投射，重现突触形成;这些细胞还表达神经标志物巢蛋白和酪氨酸羟化酶（多巴胺合成的限速酶）。全细胞膜片钳记录鉴定了中枢神经元的G蛋白偶联内向整流钾电流2通道。使用1-甲基-4-苯基-1，2，3，6-四氢吡啶诱导的PD动物模型来证明标记的HEDSC植入、迁移到损伤部位、在体内分化以及显著增加纹状体多巴胺和多巴胺代谢物浓度的能力。HEDSC是同种异体干细胞的高度可诱导来源，其在免疫活性PD小鼠模型中拯救多巴胺浓度。
Parkinson’s disease (PD) is a neurodegenerative disorder caused by the loss of dopaminergic neurons. Adult human endometrial derived stem cells (HEDSC), a readily obtainable type of mesenchymal stem-like cell, were used to generate dopaminergic cells and for transplantation. Cells expressing CD90, platelet derived growth factor (PDGF)-Rβ and CD146 but not CD45 or CD31 were differentiated in vitro into dopaminergic neurons that exhibited axon projections, pyramidal cell bodies and dendritic projections that recapitulate synapse formation; these cells also expressed the neural marker nestin and tyrosine hydroxylase, the rate-limiting enzyme in dopamine synthesis. Whole cell patch clamp recording identified G-protein coupled inwardly rectifying potassium current 2 channels characteristic of central neurons. A 1-methyl 4-phenyl 1,2,3,6-tetrahydro pyridine induced animal model of PD was used to demonstrate the ability of labelled HEDSC to engraft, migrate to the site of lesion, differentiate in vivo and significantly increase striatal dopamine and dopamine metabolite concentrations. HEDSC are a highly inducible source of allogenic stem cells that rescue dopamine concentrations in an immunocompetent PD mouse model.
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