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Generation of human neural stem cell lines and brain models of hypoxic-ischemic brain damage

人类神经干细胞系和缺氧缺血性脑损伤脑模型的生成

基本信息

批准号：
13670834
负责人：
EGUCHI Mitsuoki
金额：
$ 2.24万
依托单位：
Dokkyo University School of Medicine
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2001
资助国家：
日本
起止时间：
2001 至 2003
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13670834/
关键词：
human neural stem cells human neural crest stem cells neuronal cell death hyoxic-ischemic brain damage epilepsy hippocampus ヒト神経堤幹細胞神経幹細胞移植カイニン酸

项目摘要

We have generated self-renewing and multipotent human neural stem cells (NSCs) via retrovirus-mediated v-myc transfer into embryonic human brain cells, and have isolated several clonal cell lines. These lines can be maintained in an undifferentiated state, or induced to differentiate by changing the culture conditions. One of these cell lines, HB1/C4, is genetically modified NSCs maintained as a stable cell line in serum-free medium remains uncommited, undifferentiated, multipotent and express phenotypes specific for NSCs such as nestin, musashi and vimentin.When NB1/C4 cells were grown in a serum containing medium (5% fetal bovine serum and 5% equine serum), several differentiated cell types, which are known as progeny of NSCs such as neurons, astrocytes and oligodendrocytes were induced in culture.To investigate the fate of HB1/C4 cells in a myelin deficiency structure, we grafted NB1/C4 cells into the brain of adult or neonatal myelin mutant shiverer mouse. HB1/C4 cells were found to migrate extensively from the site of implantation into other anatomical sites and to remyelinate formerly unmyelinated axons. The ability of the HB1/C4 cells, human immortalized NSCs, to respond in vitro to guidance cues and signals that can direct their differentiation along multiple phenotypic pathways suggests that they can providea powerful and virtually unlimitted source of cells for gene cell therapy in the human neurological diseases.

我们已经通过逆转录病毒介导的v-myc基因转移到人胚胎脑细胞中产生了自我更新和多潜能的人神经干细胞(NSCs)，并分离了几个克隆细胞系。这些品系可以保持未分化状态，也可以通过改变培养条件来诱导分化。其中HB1/C4细胞系是一种转基因神经干细胞，在无血清培养中保持稳定的细胞系，在无血清培养中保持不融合、未分化、多向分化，并表达NSCs特有的表型，如巢蛋白、Musashi和vimentin。当NB1/C4细胞在含血清(5%胎牛血清和5%马血清)中生长时，在培养中诱导出几种分化的NSCs类型，如神经元、星形胶质细胞和少突胶质细胞。为了研究髓鞘结构缺陷的HB1/C4细胞的命运。HB1/C4细胞被发现从植入部位广泛迁移到其他解剖部位，并使以前的无髓鞘轴突重新髓鞘。HB1/C4细胞，即人类永生化的神经干细胞，在体外对引导它们沿多种表型途径分化的指导信号和信号的反应能力表明，它们可以为人类神经系统疾病的基因细胞治疗提供强大和几乎无限的细胞来源。