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

Characterization and gene transfer in mesenchymal stem cells derived from human umbilical-cord blood
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DOI:
10.1016/j.lab.2005.07.003
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发表时间:
2005-11-01
期刊:
JOURNAL OF LABORATORY AND CLINICAL MEDICINE
影响因子:
--
通讯作者:
Li, XK
Li, XK
中科院分区:
其他
文献类型:
--
作者:
Lu, FZ;Fujino, M;Li, XK

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已经表明,骨髓中发现的基质细胞群可以扩增并分化成具有骨、软骨、肌肉、神经和脂肪细胞表型的细胞。然而,间充质干细胞(MSC)是否存在于人类脐带血(UCB)一直是持续争论的主题。在这项研究中,我们报告了一个人口的成纤维细胞样细胞来源于单核部分的人脐带血与成骨和脂肪的潜力,以及存在的一个子集的细胞已保持在连续培养超过6个月。发现这些细胞表达CD 29、CD 44、CD 90、CD 95、CD 105、CD 166和MHC类,但不表达CD 14、CD 34、CD 40、CD 45、CD 80、CD 86、CD 117、CD 152或MHC II类。我们还比较了基因转移后的基因表达,使用慢病毒和腺病毒载体携带的绿色荧光蛋白的骨髓间充质干细胞来源于脐带血,因为需要一个可靠的基因传递系统将靶基因转移到骨髓间充质干细胞,这已经引起了人们的注意,作为潜在的平台,全身性的治疗基因传递。慢病毒载体可以比腺病毒载体更有效地转染这些细胞,并且我们维持转基因表达至少5周。这是第一个报告显示,脐血来源的MSC可以表达外源基因的慢病毒载体的方式。这些结果表明,人脐血是间充质祖细胞的来源,并可用于细胞移植和广泛的基因治疗。
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.