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用于神经疾病脑修复的基因工程化人类神经干细胞

Genetically engineered human neural stem cells for brain repair in neurological diseases.

作者信息

Kim Seung U

机构信息

Brain Disease Research Center, Ajou University School of Medicine, Suwon 442-721, Republic of Korea.

出版信息

Brain Dev. 2007 May;29(4):193-201. doi: 10.1016/j.braindev.2006.07.012. Epub 2007 Feb 15.

Abstract

Neural stem cells (NSCs)of the central nervous system (CNS) have recently received a great deal of attention and interest for their therapeutic potential for neurological disorders. NSCs are defined as CNS progenitor cells that have the capacity for self-renewal and multipotent potential to become neurons or glial cells. Recent studies have shown that NSCs isolated from mammalian CNS including human can be propagated in vitro and then implanted into the brain of animal models of human neurological disorders. Recently, we have generated clonally derived immortalized human NSC cell lines via a retroviral vector encoded with v-myc oncogene. One of the human NSC lines, HB1.F3, was utilized in stem-cell based therapy in animal models of human neurological disorders. When F3 human NSCs were implanted into the brain of murine models of lysosomal storage diseases, stroke, Parkinson disease, Huntington disease or stroke, implanted F3 NSCs were found to migrate to the lesion sites, differentiate into neurons and glial cells, and restore functional deficits found in these neurological disorders. In animal models of brain tumors, F3 NSCs could deliver a bioactive therapeutically relevant molecules to effect a significant anti-tumor response intracranial tumor mass. Since these genetically engineered human NSCs are immortalized and continuously multiplying, there would be limitless supply of human neurons for treatment for patients suffering from neurological disorders including stroke, Parkinson disease, Huntington disease, ALS, multiple sclerosis and spinal cord injury. The promising field of stem cell research as it applies to regenerative medicine is still in infancy, but its potential appears limitless, and we are blessed to be involved in this exciting realm of research.

摘要

中枢神经系统(CNS)的神经干细胞(NSCs)因其对神经系统疾病的治疗潜力,近来受到了广泛关注。神经干细胞被定义为中枢神经系统的祖细胞,具有自我更新能力以及分化为神经元或神经胶质细胞的多能潜力。最近的研究表明,从包括人类在内的哺乳动物中枢神经系统分离出的神经干细胞能够在体外增殖,然后植入人类神经系统疾病动物模型的大脑中。最近,我们通过编码v-myc癌基因的逆转录病毒载体,建立了克隆衍生的永生化人类神经干细胞系。其中一个人类神经干细胞系HB1.F3,被用于人类神经系统疾病动物模型的干细胞治疗。当将F3人类神经干细胞植入溶酶体贮积病、中风、帕金森病、亨廷顿病或脑肿瘤的小鼠模型大脑中时,发现植入的F3神经干细胞会迁移到损伤部位,分化为神经元和神经胶质细胞,并恢复这些神经系统疾病中出现的功能缺陷。在脑肿瘤动物模型中,F3神经干细胞能够递送具有生物活性的治疗相关分子,从而对颅内肿瘤块产生显著的抗肿瘤反应。由于这些基因工程改造的人类神经干细胞是永生化且能持续增殖的,因此对于患有包括中风、帕金森病、亨廷顿病、肌萎缩侧索硬化症、多发性硬化症和脊髓损伤在内的神经系统疾病的患者而言,将有无限供应的人类神经元用于治疗。干细胞研究应用于再生医学这一充满前景的领域仍处于起步阶段,但其潜力似乎是无限的,我们很幸运能够参与到这个令人兴奋的研究领域。

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