Identification of Human Placenta-Derived Mesenchymal Stem Cells Involved in Re-Endothelialization

Identification of Human Placenta-Derived Mesenchymal Stem Cells Involved in Re-Endothelialization
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DOI:
10.1002/jcp.22329
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发表时间:
2011-01-01
影响因子:
5.6
通讯作者:
Ohneda, Osamu
Ohneda, Osamu
中科院分区:
生物学2区
文献类型:
--
作者:
Tran, Tu Cam;Kimura, Kenichi;Ohneda, Osamu

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人胎盘是再生医学间充质干细胞(MSC)的一个有吸引力的来源。MSC上表达的细胞表面标志物已被提议作为用于从其他细胞群中分离MSC的有用工具。然而,MSC标志物的表达和支持体内组织再生的能力之间的相关性尚未得到很好的研究。在这里,我们建立了几个人胎盘间充质干细胞系,并检查他们的细胞表面标志物的表达和他们的能力,向间充质细胞谱系分化。我们发现,CD 349/frizzled-9的表达,Wnt配体的受体,是阳性的胎盘来源的MSC。因此,我们从MSC系中分离出CD 349阴性和阳性组分,并使用小鼠模型研究细胞移植如何成功修复骨折骨和恢复缺血区域的血流。在小鼠移植实验中,CD 349阴性和阳性细胞显示出相似的细胞表面标志物表达模式,并促进了骨折骨的修复。有趣的是,CD 349阴性而非CD 349阳性细胞显示出对血管闭塞后恢复血流的显著作用。我们发现,在CD 349阴性细胞中,缺氧诱导PDGF β和bFGF mRNA的表达高于CD 349阳性细胞,而VEGF的表达在CD 349阴性和CD 349阳性细胞中没有显著差异。这些发现表明,CD 349可用作MSC分离的再内皮化的专门标记物的可能性。J.细胞。226:224-235,2010。(C)2010 Wiley-Liss,Inc.
Human placenta is an attractive source of mesenchymal stem cells (MSC) for regenerative medicine. The cell surface markers expressed on MSC have been proposed as useful tools for the isolation of MSC from other cell populations. However, the correlation between the expression of MSC markers and the ability to support tissue regeneration in vivo has not been well examined. Here, we established several MSC lines from human placenta and examined the expression of their cell surface markers and their ability to differentiate toward mesenchymal cell lineages. We found that the expression of CD349/frizzled-9, a receptor for Wnt ligands, was positive in placenta-derived MSC. So, we isolated CD349-negative and -positive fractions from an MSC line and examined how successfully cell engraftment repaired fractured bone and recovered blood flow in ischemic regions using mouse models. CD349-negative and -positive cells displayed a similar expression pattern of cell surface markers and facilitated the repair of fractured bone in transplantation experiments in mice. Interestingly, CD349-negative, but not CD349-positive cells, showed significant effects on recovering blood flow following vascular occlusion. We found that induction of PDGF beta and bFGF mRNAs by hypoxia was greater in CD349-negative cells than in CD349-positive cells while the expression of VEGF was not significantly different in CD349-negative and CD349-positive cells. These findings suggest the possibility that CD349 could be utilized as a specialized marker for MSC isolation for re-endothelialization. J. Cell. Physiol. 226: 224-235, 2010. (C) 2010 Wiley-Liss, Inc.