人脐带血间充质干细胞的特性和基因转移

Fei-Zhou Lu , Masayuki Fujino , Yusuke Kitazawa , Taro Uyama , Yuko Hara , Naoko Funeshima , Jian-Yuan Jiang , Akihiro Umezawa , Xiao-Kang Li
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引用次数: 51

摘要

研究表明,骨髓中发现的基质细胞群可以扩增并分化为具有骨、软骨、肌肉、神经和脂肪细胞表型的细胞。然而,间充质干细胞(MSCs)是否存在于人脐带血(UCB)中一直是争论的主题。在这项研究中,我们报道了从人UCB单核部分提取的成纤维细胞样细胞群,这些细胞具有成骨和成脂肪的潜力,以及在连续培养中维持超过6个月的细胞亚群的存在。这些细胞表达CD29、CD44、CD90、CD95、CD105、CD166和MHC类,但不表达CD14、CD34、CD40、CD45、CD80、CD86、CD117、CD152或MHC II类。我们还比较了使用携带绿色荧光蛋白的慢体病毒和腺病毒载体将基因转移到来自UCB的间充质干细胞后的基因表达,因为将靶基因转移到间充质干细胞需要可靠的基因传递系统,这已经成为系统递送治疗基因的潜在平台。慢病毒载体比腺病毒载体更有效地转导这些细胞,并且我们将转基因表达维持了至少5周。这是首次报道显示ucb衍生的MSCs可以通过慢病毒载体表达外源基因。这些结果表明,人UCB是间充质祖细胞的来源,可用于细胞移植和广泛的基因治疗。
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Characterization and gene transfer in mesenchymal stem cells derived from human umbilical-cord blood

It has been shown that the stromal-cell population found in bone marrow can be expanded and differentiated into cells with the phenotypes of bone, cartilage, muscle, neural, and fat cells. However, whether mesenchymal stem cells (MSCs) are present in human umbilical-cord blood (UCB) has been the subject of ongoing debate. In this study, we report on a population of fibroblastlike cells derived from the mononuclear fraction of human UCB with osteogenic and adipogenic potential, as well as the presence of a subset of cells that have been maintained in continuous culture for more than 6 months. These cells were found to express CD29, CD44, CD90, CD95, CD105, CD166, and MHC class, but not CD14, CD34, CD40, CD45, CD80, CD86, CD117, CD152, or MHC class II. We also compared gene expression after gene transfer using lenti- and adenoviral vectors carrying the green fluorescence protein to the MSCs derived from UCB because a reliable gene-delivery system is required to transfer target genes into MSCs, which have attracted attention as potential platforms for the systemic delivery of therapeutic genes. The lentiviral vectors can transduce these cells more efficiently than can adenoviral vectors, and we maintained transgene expression for at least 5 weeks. This is the first report showing that UCB-derived MSCs can express exogenous genes by way of a lentivirus vector. These results demonstrate that human UCB is a source of mesenchymal progenitors and may be used in cell transplantation and a wide range of gene-therapy treatments.

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