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源自人脐带血的间充质干细胞的特性鉴定与基因转移

Characterization and gene transfer in mesenchymal stem cells derived from human umbilical-cord blood.

作者信息

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

机构信息

Laboratory of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan.

出版信息

J Lab Clin Med. 2005 Nov;146(5):271-8. doi: 10.1016/j.lab.2005.07.003.

DOI:10.1016/j.lab.2005.07.003
PMID:16242526
Abstract

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.

摘要

研究表明,骨髓中的基质细胞群体能够扩增并分化为具有骨细胞、软骨细胞、肌肉细胞、神经细胞和脂肪细胞表型的细胞。然而,人脐带血(UCB)中是否存在间充质干细胞(MSCs)一直是一个存在争议的话题。在本研究中,我们报告了一群源自人UCB单核部分的成纤维细胞样细胞,它们具有成骨和成脂潜能,并且存在一群在连续培养中维持了6个月以上的细胞。这些细胞被发现表达CD29、CD44、CD90、CD95、CD105、CD166和MHC I类分子,但不表达CD14、CD34、CD40、CD45、CD80、CD86、CD117、CD152或MHC II类分子。我们还比较了使用携带绿色荧光蛋白的慢病毒和腺病毒载体进行基因转移后,UCB来源的MSCs中的基因表达情况,因为需要一个可靠的基因递送系统将靶基因转移到MSCs中,而MSCs作为治疗性基因全身递送的潜在平台已引起关注。慢病毒载体比腺病毒载体能更有效地转导这些细胞,并且我们使转基因表达维持了至少5周。这是首次报道UCB来源的MSCs能够通过慢病毒载体表达外源基因。这些结果表明,人UCB是间充质祖细胞的一个来源,可用于细胞移植和广泛的基因治疗。

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