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子宫内膜干细胞移植可恢复帕金森病模型中的多巴胺产生。

Endometrial stem cell transplantation restores dopamine production in a Parkinson's disease model.

机构信息

Department of Obstetrics, Gynecology and Reproductive Sciences, Yale University School of Medicine, New Haven, CT, USA.

出版信息

J Cell Mol Med. 2011 Apr;15(4):747-55. doi: 10.1111/j.1582-4934.2010.01068.x.

Abstract

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.

摘要

帕金森病(PD)是一种由多巴胺能神经元丧失引起的神经退行性疾病。成人子宫内膜来源的干细胞(HEDSC)是一种易于获得的间充质样干细胞,可用于产生多巴胺能细胞并进行移植。在体外表达 CD90、血小板衍生生长因子(PDGF)-Rβ和 CD146 但不表达 CD45 或 CD31 的细胞分化为多巴胺能神经元,表现出轴突投射、金字塔形细胞体和树突状投射,再现了突触形成;这些细胞还表达神经标记物巢蛋白和酪氨酸羟化酶,这是多巴胺合成的限速酶。全细胞膜片钳记录鉴定出 G 蛋白偶联内向整流钾通道 2,这是中枢神经元的特征。使用 1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的 PD 动物模型证明了标记的 HEDSC 能够植入、迁移到病变部位、在体内分化,并显著增加纹状体多巴胺和多巴胺代谢物浓度。HEDSC 是一种高度可诱导的同种异体干细胞来源,可以挽救免疫功能正常的 PD 小鼠模型中的多巴胺浓度。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/319e/3922663/6d650161bd5d/jcmm0015-0747-f1.jpg

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