Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood

Comparative characteristics of mesenchymal stem cells from human bone marrow, adipose tissue, and umbilical cord blood
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DOI:
10.1016/j.exphem.2005.07.003
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发表时间:
2005-11-01
影响因子:
2.6
通讯作者:
Ho, AD
Ho, AD
中科院分区:
医学4区
文献类型:
--
作者:
Wagner, W;Wein, F;Ho, AD

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目标。已经提出了各种制备方案来获取和培养间充质干细胞(MSC)。虽然表面抗原标记物未能准确定义这一群体,但微阵列分析可能提供一种更好的工具来表征多发性硬化症。在这项研究中,我们分析了从脂肪组织(AT)、脐带血(CB)和骨髓(BM)分离的人MSC在两种生长条件下的整体基因表达谱,并与终末分化的人成纤维细胞(HS68)进行了比较。使用我们的人类基因组微阵列对51.144个不同的cDNA克隆进行比较。在适当的培养条件下,所有的MSC均可分化为成骨和成脂,而成纤维细胞则不能。使用一组22个表面抗原标记物的流式细胞术没有观察到表型差异。来自不同供体的MSC在相同的培养过程中产生了一致的、可重复性的基因表达谱,而来自不同个体发育来源或不同培养条件的MSC中许多基因的表达存在差异。与HS68成纤维细胞相比,来自AT、CB和BM的所有MSC标本中有25个基因重叠和上调。这些基因包括纤维连接蛋白、ECM2、Glypcan-4、ID1、NF1B、HOXA5和HOXB6。MSC中上调的许多基因参与细胞外基质、形态发生和发育,而Wnt通路的几种抑制因子(Dkk1、DKK3、SFRP1)在成纤维细胞中高表达。我们的研究结果为利用基因分型分析确定MSC的重复性和可靠性的质量控制提供了基础。(C)2005年国际实验血液学学会。
Objective. Various preparative protocols have been proposed for the acquisition and cultivation of mesenchymal stem cells (MSC). Whereas surface antigen markers have failed to precisely define this population, microarray analysis might provide a better tool for characterization of MSC.Methods. In this study, we have analyzed global gene expression profiles of human MSC isolated from adipose tissue (AT), from umbilical cord blood (CB), and from bone marrow (BM) under two growth conditions and have compared them to terminally differentiated human fibroblasts (HS68). Profiles were compared using our Human Genome Microarray representing 51.144 different cDNA clones.Results. Cultured with the appropriate conditions, osteogenic and adipogenic differentiation could be confirmed in all MSC preparations but not in fibroblasts. No phenotypic differences were observed by flow cytometry using a panel of 22 surface antigen markers. Whereas MSC derived from different donors using the same culture procedure yielded a consistent and reproducible gene expression profile, many genes were differentially expressed in MSC from different ontogenetic sources or from different culture conditions. Twenty-five genes were overlapping and upregulated in all MSC preparations from AT, CB, and BM as compared to HS68 fibroblasts. These genes included fibronectin, ECM2, glypican-4, ID1, NF1B, HOXA5, and HOXB6. Many genes upregulated in MSC are involved in extracellular matrix, morphogenesis, and development, whereas several inhibitors of the Wnt pathway (DKK1, DKK3, SFRP1) were highly expressed in fibroblasts.Conclusion. Our results have provided a foundation for a more reproducible and reliable quality control using genotypic analysis for defining MSC. (c) 2005 International Society for Experimental Hematology.