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首页> 外文期刊>Cell and Tissue Research >Defining essential stem cell characteristics in adipose-derived stromal cells extracted from distinct anatomical sites
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Defining essential stem cell characteristics in adipose-derived stromal cells extracted from distinct anatomical sites

机译:定义从不同解剖部位提取的脂肪基质细胞的基本干细胞特征

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The discovery of adipose-derived stromal cells (ASCs) has created many opportunities for the development of patient-specific cell-based replacement therapies. We have isolated multiple cell strains of ASCs from various anatomical sites (abdomen, arms/legs, breast, buttocks), indicating widespread distribution of ASCs throughout the body. Unfortunately, there exists a general lack of agreement in the literature as to their “stem cell” characteristics. We find that telomerase activity and expression of its catalytic subunit in ASCs are both below the levels of detection, independent of age and culturing conditions. ASCs also undergo telomere attrition and eventually senesce, while maintaining a stable karyotype without the development of spontaneous tumor-associated abnormalities. Using a set of cell surface markers that have been promoted to identify ASCs, we find that they failed to distinguish ASCs from normal fibroblasts, as both are positive for CD29, CD73 and CD105 and negative for CD14, CD31 and CD45. All of the ASC isolates are multipotent, capable of differentiating into osteocytes, chondrocytes and adipocytes, while fibroblasts show no differentiation potential. Our ASC strains also show elevated expression of genes associated with pluripotent cells, Oct-4, SOX2 and NANOG, when compared to fibroblasts and bone marrow-derived mesenchymal stem cells (BM-MSCs), although the levels were lower than induced pluripotent stem cells (iPS). Together, our data suggest that, while the cell surface profile of ASCs does not distinguish them from normal fibroblasts, their differentiation capacity and the expression of genes closely linked to pluripotency clearly define ASCs as multipotent stem cells, regardless of tissue isolation location.
机译:脂肪基质细胞(ASCs)的发现为开发患者特异性的基于细胞的替代疗法创造了许多机会。我们从各个解剖部位(腹部,手臂/腿,乳房,臀部)分离了多种ASCs细胞株,表明ASCs在人体中广泛分布。不幸的是,文献中普遍缺乏关于它们的“干细胞”特征的共识。我们发现,端粒酶活性及其催化亚基在ASC中的表达均低于检测水平,与年龄和培养条件无关。 ASC还经历端粒磨损并最终衰老,同时保持稳定的核型,而不会发生自发的肿瘤相关异常。使用一组已被促进鉴定ASC的细胞表面标记,我们发现它们未能将ASC与正常成纤维细胞区分开,因为CD29,CD73和CD105均为阳性,而CD14,CD31和CD45均为阴性。所有的ASC分离物都是多能的,能够分化为骨细胞,软骨细胞和脂肪细胞,而成纤维细胞则没有分化潜能。与成纤维细胞和骨髓源性间充质干细胞(BM-MSC)相比,我们的ASC菌株还显示了与多能细胞,Oct-4,SOX2和NANOG相关的基因表达升高,尽管该水平低于诱导的多能干细胞(iPS)。总之,我们的数据表明,尽管ASC的细胞表面轮廓无法将它们与正常的成纤维细胞区分开,但它们的分化能力和与多能性紧密相关的基因表达清楚地将ASC定义为多能干细胞,而与组织分离位置无关。

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