Stage-specific embryonic antigen-4 identifies human dental pulp stem cells

Stage-specific embryonic antigen-4 identifies human dental pulp stem cells
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DOI:
10.1016/j.yexcr.2012.01.008
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发表时间:
2012-03-10
影响因子:
3.7
通讯作者:
Yamashiro, Takashi
Yamashiro, Takashi
中科院分区:
医学3区
文献类型:
--
作者:
Kawanabe, Noriaki;Murata, Satoko;Yamashiro, Takashi

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胚胎干细胞相关抗原在多种成体干细胞和胚胎干细胞中表达。在本研究中,我们研究了阶段特异性胚胎抗原(SSEA)-4是否可以用于分离牙髓(DP)干细胞。DP细胞表现出与间充质干细胞(MSC)相似的可塑性粘附、特异性表面抗原表达和多能分化潜能。体外培养的DP细胞和体内DP组织中均发现SSEA-4+细胞。流式细胞术分析显示45.5%的DP细胞为SSEA-4+。在全反式维甲酸的作用下培养DP细胞,观察到SSEA-3和SSEA-4明显下调,SSEA-1上调。与未门控细胞和SSEA-4 -细胞相比,SSEA-4+ DP细胞的端粒长度更长,生长速度更快。克隆实验表明,65.5%的SSEA-4+ DP细胞具有成骨潜能,SSEA-4+克隆DP细胞在体外具有向成骨细胞、软骨细胞和神经元的多系分化潜能。此外,SSEA-4+ DP细胞在体内具有异位骨形成能力。因此,我们的研究结果表明SSEA-4是一种特异性的细胞表面抗原,可用于鉴定DP干细胞。(C) 2012爱思唯尔公司版权所有。
Embryonic stem cell-associated antigens are expressed in a variety of adult stem cells as well as embryonic stem cells. In the present study, we investigated whether stage-specific embryonic antigen (SSEA)-4 can be used to isolate dental pulp (DP) stem cells. DP cells showed plastic adherence, specific surface antigen expression, and multipotent differentiation potential, similar to mesenchymal stem cells (MSC). SSEA-4+ cells were found in cultured DP cells in vitro as well as in DP tissue in vivo. Flow cytometric analysis demonstrated that 45.5% of the DP cells were SSEA-4+. When the DP cells were cultured in the presence of all-trans-retinoic acid, marked downregulation of SSEA-3 and SSEA-4 and the upregulation of SSEA-1 were observed. SSEA-4+ DP cells showed a greater telomere length and a higher growth rate compared to ungated and SSEA-4 - cells. A clonal assay demonstrated that 65.5% of the SSEA-4+ DP cells had osteogenic potential, and the SSEA-4+ clonal DP cells showed multilineage differentiation potential toward osteoblasts, chondrocytes, and neurons in vitro. In addition, the SSEA-4+ DP cells had the capacity to form ectopic bone in vivo. Thus, our results suggest that SSEA-4 is a specific cell surface antigen that can be used to identify DP stem cells. (C) 2012 Elsevier Inc. All rights reserved.