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牙髓细胞具有通过多巴胺能神经元分化治疗帕金森病的潜力。

Dental follicle cells show potential for treating Parkinson's disease through dopaminergic-neuronogenic differentiation.

机构信息

Engineering Research Center of Oral Translational Medicine, Ministry of Education, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

National Engineering Laboratory for Oral Regenerative Medicine, West China Hospital of Stomatology, Sichuan University, Chengdu, China.

出版信息

Hum Cell. 2022 Nov;35(6):1708-1721. doi: 10.1007/s13577-022-00774-6. Epub 2022 Aug 30.

Abstract

Among all the adult stem cells, odontogenic stem cells inherit the characterization of neurogenic potential of their precursor ones-the cranial crest cells. Dental follicle cells (DFCs), one of the special kind of odontogenic stem cells, are raising interest in applying to regenerative medicine for they possess multi-differentiation potential, relatively free access and ethic-friendly characteristic. Parkinson's disease (PD), as one of the common neurodegenerative disorders, affects about 0.3% of the general population. Stem cell therapies are thought to be effective to treat it. Aiming at tackling ethical-concernings, confined sources and practically applicational limits, we made use of dopaminergic neurongenic differentiation potential of the DFCs and dedicated every effort to applying them as promising cell source for treating PD. Dental follicle cells were cultured from human dental follicle tissues collected from 12 to 18-year-old teenagers' completely impacted third molars. Our data demonstrated that hDFCs were expressing mesenchymal stem cell-associated surface markers, and possessed the ability of osteogenic, adipogenic and neurogenic differentiation in vitro. Additionally, hDFCs formed neuron-like cells in vitro and in vivo, as well as expressing dopaminergic-neuronogenic marker-TH. Moreover, hDFCs survived in the transplanted areas of the Parkinson's disease model of mouse over six weeks post-surgery, and the number of TH-positive DFCs in the DFCs-Grafted group surpassed its counterpart of the MPTP group with statistically significant difference. This study indicated that hDFCs might be a promising source of dopaminergic neurons for functional transplantation, and encouraged further detailed studies on the potential of hDFCs for treating PD.

摘要

在所有的成体干细胞中,牙源性干细胞继承了其前体细胞——颅嵴细胞的神经发生潜力特征。牙囊细胞(DFC)是一种特殊的牙源性干细胞,具有多向分化潜能、相对容易获得和伦理友好的特点,因此在再生医学中的应用受到关注。帕金森病(PD)是一种常见的神经退行性疾病,影响约 0.3%的普通人群。人们认为干细胞疗法对其有效。为了解决与伦理、来源有限和实际应用限制相关的问题,我们利用了 DFC 的多巴胺能神经发生分化潜能,并努力将其作为治疗 PD 的有前途的细胞来源。从 12 至 18 岁青少年完全埋伏第三磨牙的牙囊组织中培养牙囊细胞。我们的数据表明,hDFC 表达间充质干细胞相关表面标志物,并具有体外成骨、成脂和神经分化的能力。此外,hDFC 在体外和体内形成神经元样细胞,并表达多巴胺能神经元标志物-TH。此外,hDFC 在帕金森病模型小鼠的移植部位存活超过 6 周,并且 hDFC 移植组中 TH 阳性 DFC 的数量明显高于 MPTP 组。这项研究表明,hDFC 可能是功能性移植中多巴胺能神经元的有前途的来源,并鼓励进一步研究 hDFC 治疗 PD 的潜力。

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