LNGFR(+)THY-1(+)VCAM-1(hi+) cells reveal functionally distinct subpopulations in mesenchymal stem cells.

LNGFR(+)THY-1(+)VCAM-1(hi+) cells reveal functionally distinct subpopulations in mesenchymal stem cells.
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DOI:
10.1016/j.stemcr.2013.06.001
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发表时间:
2013
期刊:
影响因子:
5.9
通讯作者:
Matsuzaki, Yumi
Matsuzaki, Yumi
中科院分区:
医学1区
文献类型:
--
作者:
Mabuchi, Yo;Morikawa, Satoru;Harada, Seiko;Niibe, Kunimichi;Suzuki, Sadafumi;Renault-Mihara, Francois;Houlihan, Diarmaid D.;Akazawa, Chihiro;Okano, Hideyuki;Matsuzaki, Yumi

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人类间充质干细胞(hMSCs),这是传统上分离的基础上,他们坚持塑料,是异质的,具有不良的生长和分化,限制了我们的能力,以研究其内在特性。我们报告了一种改进的前瞻性克隆分离技术,并揭示了三种细胞表面标志物(LNGFR,THY-1和VCAM-1)的组合允许选择高度富集的克隆细胞(三个分离的细胞中的一个)。LNGFR+THY-1+细胞的克隆表征证实了克隆之间的细胞异质性。快速扩增克隆(RECs)表现出强大的多系分化和自我更新能力,而其他克隆往往通过P16 INK 4a获得细胞衰老,并表现出频繁的基因组错误。此外,与其他克隆相比,RECs表现出独特的VCAM-1表达和更高的细胞运动性。组合标记LNGFR+THY-1+VCAM-1hi+(LTV)可选择性地用于分离最有效和遗传稳定的MSC。人骨髓中LNGFR+THY-1+群体显著富集CFU-Fs快速扩增克隆(RECs)表现出干细胞样特征VCAM-1的表达与增殖和迁移能力相关组合标志物LNGFR+THY-1+VCAM-1hi+可用于分离多能MSC
Human mesenchymal stem cells (hMSCs), which conventionally are isolated based on their adherence to plastic, are heterogeneous and have poor growth and differentiation, limiting our ability to investigate their intrinsic characteristics. We report an improved prospective clonal isolation technique and reveal that the combination of three cell-surface markers (LNGFR, THY-1, and VCAM-1) allows for the selection of highly enriched clonogenic cells (one out of three isolated cells). Clonal characterization of LNGFR+THY-1+ cells demonstrated cellular heterogeneity among the clones. Rapidly expanding clones (RECs) exhibited robust multilineage differentiation and self-renewal potency, whereas the other clones tended to acquire cellular senescence via P16INK4a and exhibited frequent genomic errors. Furthermore, RECs exhibited unique expression of VCAM-1 and higher cellular motility compared with the other clones. The combination marker LNGFR+THY-1+VCAM-1hi+ (LTV) can be used selectively to isolate the most potent and genetically stable MSCs. The LNGFR+THY-1+ population is significantly enriched for CFU-Fs in human bone marrow Rapidly expanding clones (RECs) exhibited stem-like characteristics Expression of VCAM-1 correlated with proliferation and migration ability The combination marker LNGFR+THY-1+VCAM-1hi+ is useful for isolating multipotent MSCs
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