Multilineage potential of stable human mesenchymal stem cell line derived from fetal marrow.
Multilineage potential of stable human mesenchymal stem cell line derived from fetal marrow.
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DOI：
10.1371/journal.pone.0001272
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发表时间：
2007-12-05
期刊：
影响因子：
3.7
通讯作者：
Kim, Seung U.
中科院分区：
文献类型：
--
作者：
Nagai, Atsushi;Kim, Woo K.;Lee, Hong J.;Jeong, Han S.;Kim, Kwang S.;Hong, Seok H.;Park, In H.;Kim, Seung U.
人类骨髓包含两种主要的细胞类型：造血干细胞（hsc）和间充质干细胞（MSCs）。MSCs具有自我更新能力和多能性，可以分化为成骨细胞、软骨细胞、脂肪细胞和肌肉细胞。在体外和体内，MSCs移植到包括缺血和脑出血（ICH）中风在内的神经系统疾病动物模型的大脑后，也被称为分化为神经元和胶质细胞。为了获得足够数量和均匀的人骨髓间充质干细胞群体，我们用编码v-myc基因的逆转录病毒载体转染胎人骨髓间充质干细胞原代细胞培养物，克隆分离出永久稳定的人骨髓间充质干细胞系。其中一个细胞系，HM3。通过RT-PCR检测神经干细胞（nestin和Musashi1）、神经元（神经丝蛋白、突触素和MAP2）、星形胶质细胞（胶质纤维酸性蛋白，GFAP）和少突胶质细胞（髓鞘碱性蛋白，MBP）遗传标记的表达，发现B10 （B10）在体外分化为神经干细胞、神经元、星形胶质细胞和少突胶质细胞。此外，B10细胞分化为神经细胞类型，如免疫细胞学显示巢蛋白（用于神经干细胞）、神经丝蛋白和β-微管蛋白III（神经元）、GFAP（星形胶质细胞）和半乳糖脑苷（少突胶质细胞）。脑移植小鼠脑中风模型后，B10人间充质干细胞融入宿主脑存活，分化为神经元和星形胶质细胞，并诱导脑中风动物行为改善。B10人MSC细胞系不仅为器官发生特别是神经发生的研究提供了有用的工具，而且为中风和其他神经系统疾病动物模型的细胞治疗研究提供了宝贵的细胞来源。
Human bone marrow contains two major cell types, hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs). MSCs possess self-renewal capacity and pluripotency defined by their ability to differentiate into osteoblasts, chondrocytes, adipocytes and muscle cells. MSCs are also known to differentiate into neurons and glial cells in vitro, and in vivo following transplantation into the brain of animal models of neurological disorders including ischemia and intracerebral hemorrhage (ICH) stroke. In order to obtain sufficient number and homogeneous population of human MSCs, we have clonally isolated permanent and stable human MSC lines by transfecting primary cell cultures of fetal human bone marrow MSCs with a retroviral vector encoding v-myc gene. One of the cell lines, HM3.B10 (B10), was found to differentiate into neural cell types including neural stem cells, neurons, astrocytes and oligodendrocytes in vitro as shown by expression of genetic markers for neural stem cells (nestin and Musashi1), neurons (neurofilament protein, synapsin and MAP2), astrocytes (glial fibrillary acidic protein, GFAP) and oligodendrocytes (myelin basic protein, MBP) as determined by RT-PCR assay. In addition, B10 cells were found to differentiate into neural cell types as shown by immunocytochical demonstration of nestin (for neural stem cells), neurofilament protein and β-tubulin III (neurons) GFAP (astrocytes), and galactocerebroside (oligodendrocytes). Following brain transplantation in mouse ICH stroke model, B10 human MSCs integrate into host brain, survive, differentiate into neurons and astrocytes and induce behavioral improvement in the ICH animals. B10 human MSC cell line is not only a useful tool for the studies of organogenesis and specifically for the neurogenesis, but also provides a valuable source of cells for cell therapy studies in animal models of stroke and other neurological disorders.
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