您当前的位置:首页 >> 历史
【科技前瞻】Eur J Neurosci:干细胞经基因编辑有望用于治疗帕金森病
发布时间:2019-09-04
 

在英国,帕金森病的发病率大约为1/350,严重影响着人们的生活质量。近日,在一项新的研究中,来自英国爱丁堡大学和UCB制药公司的研究人员在改善帕金森病的细胞替代疗法上迈出了关键一步。

在这项新的研究中,研究人员构建出对帕金森病有抵抗力的人胚胎干细胞(human embryonic stem cells,hESC)。具体而言,他们利用CRISPR/Cas9n技术切除hESC中的DNA片段。在这个过程中,他们剔除了与有毒性的团块,即路易小体形成相关的基因SNCA,这种毒性团块形成是帕金森患者脑细胞的一种典型特征。在实验室测试中,这些干细胞在培养皿中可被转化为产生多巴胺的神经元。研究人员发现相比于未经过基因编辑的神经元,经过基因编辑的神经元并没有形成有毒性团块。研究人员表示,这一进展可能对患有帕金森病的年轻患者和患有侵袭性帕金森病的患者最有益,但还需开展进一步的临床试验。

研究人员Tilo Kunath博士表示,帕金森病在神经元之间进行扩散并侵入健康细胞,希望这种涉及将健康细胞移植到被帕金森病破坏的大脑区域中的疗法能够缓解震颤和平衡问题等症状。帕金森病治愈基金会研究副主任Simon Stott博士也肯定了这一研究的重要意义。



推荐阅读原文:
Engineering synucleinopathy-resistant human dopaminergic neurons by CRISPR-mediated deletion of the SNCA gene.

An emerging treatment for Parkinson's disease (PD) is cell replacement therapy. Authentic midbrain dopaminergic (mDA) neuronal precursors can be differentiated from human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs). These laboratory-generated mDA cells have been demonstrated to mature into functional dopaminergic neurons upon transplantation into preclinical models of PD. However, clinical trials with human fetal mesenchephalic cells have shown that cell replacement grafts in PD are susceptible to Lewy body formation suggesting host-to-graft transfer of α-synuclein pathology. Here, we have used CRISPR/Cas9n technology to delete the endogenous SNCA gene, encoding for α-synuclein, in a clinical-grade hESC line to generate SNCA+/− and SNCA−/− cell lines. These hESC lines were first differentiated into mDA neurons, and then challenged with recombinant α-synuclein preformed fibrils (PFFs) to seed the formation for Lewy-like pathology as measured by phosphorylation of serine-129 of α-synuclein (pS129-αSyn). Wild-type neurons were fully susceptible to the formation of protein aggregates positive for pS129-αSyn, while SNCA+/− and SNCA−/− neurons exhibited significant resistance to the formation of this pathological mark. This work demonstrates that reducing or completely removing SNCA alleles by CRISPR/Cas9n-mediated gene editing confers a measure of resistance to Lewy pathology.




中国干细胞集团有限公司

www.chinacordblood.org

400-675-5599


中国干细胞集团上海大厦

地址:上海市新冠路99号

电话:021-3918-8888

传真:021-3918-9999

邮编:201815


中国干细胞集团重庆大厦

地址:重庆市两江新区云汉大道299号

电话:023-6398-8888

传真:023-6398-9999

邮编:400714


中国干细胞集团博鳌大厦

地址:海南博鳌乐城国际医疗旅游先行区乐颐大道9号

电话:0898-6292-8888

传真:0898-6292-0999

邮编:571435


长按关注上海市脐带血库官方微信

长按关注中国干细胞集团官方微信

长按关注中国干细胞集团服务号

长按关注中国干细胞集团附属干细胞医院官方微信

相关阅读