Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo
Multipotential human adipose-derived stromal stem cells exhibit a perivascular phenotype in vitro and in vivo
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DOI：
10.1002/jcp.21210
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发表时间：
2008-02-01
影响因子：
5.6
通讯作者：
Gronthos, S.
中科院分区：
文献类型：
--
作者：
Zannettino, A. C. W.;Paton, S.;Gronthos, S.
在不同组织中发现的间充质干细胞样细胞位于血管周围的微环境中。在本研究中，我们使用与间充质细胞和血管周围细胞相关的标志物，包括STRO - 1、CID146和3G5，对脂肪来源的基质/干细胞（ASCs）的假定微环境进行了研究。对人脂肪组织切片进行免疫荧光染色显示，STRO - 1和3G5与CID146共定位在血管的血管周围区域。流式细胞术（FACS）被用于确定CID146、3G5和STRO - 1特异性单克隆抗体从分离的人脂肪组织中分离出具有克隆形成能力的ASCs的能力。发现克隆形成的成纤维细胞集落（CFU - F）在那些用STRO - 1、CID146或3G5选择的细胞组分中富集。流式细胞术分析显示，培养的ASCs在与基质细胞（CD44、CD90、CD105、CD106、CD146、CD166、STRO - 1、碱性磷酸酶）、内皮细胞（CD31、CD105、CD106、CD146、CD166）、造血细胞（CD14、CD31、CD45）和血管周围细胞（3G5、STRO - 1、CD146）相关的细胞表面标志物表达方面表现出相似的表型特征。免疫选择的ASCs群体保持了其特征性的多潜能特性，这体现在它们在体外形成茜素红阳性矿化沉积物、油红O阳性脂滴和阿尔辛蓝阳性富含蛋白聚糖的基质的能力上。此外，从STRO - 1、3G5或CD146选择的细胞群体建立的ASCs培养物，当皮下移植到NOD/SCID小鼠体内时，都能够形成异位骨。这里呈现的研究结果描述了成年人类脂肪组织内的一个多潜能干细胞群体，它似乎与血管周围的血管周围细胞密切相关。
Mesenchymal stem-like cells identified in different tissues reside in a perivascular niche. In the present study, we investigated the putative niche of adipose-derived stromal/stem cells (ASCs) using markers, associated with mesenchymal and perivascular cells, including STRO-1, CID 146, and 3G5. Immunofluorescence staining of human adipose tissue sections, revealed that STRO-1 and 3G5 co-localized with CID 146 to the perivascular regions of blood vessels. FACS was used to determine the capacity of the CID 146, 3G5, and STRO-1 specific monoclonal antibodies to isolate clonogenic ASCs from disassociated human adipose tissue. Clonogenic fibroblastic colonies (CFU-F) were found to be enriched in those cell fractions selected with either STRO-1, CID 146, or 3G5. Flow cytometric analysis revealed that cultured ASCs exhibited similar phenotypic profiles in relation to their expression of cell surface markers associated with stromal cells (CD44, CD90, CD105, CD106, CD146, CD166, STRO-1, alkaline phosphatase), endothelial cells (CD31, CD105, CD106, CD146, CD166), haematopoietic cells (CD14, CD31, CD45), and perivascular cells (3G5, STRO-1, CD146). The immunoselected ASCs populations maintained their characteristic multipotential properties as shown by their capacity to form Alizarin Red positive mineralized deposits, Oil Red O positive lipid droplets, and Alcian Blue positive proteoglycan-rich matrix in vitro. Furthermore, ASCs cultures established from either STRO-1, 3G5, or CD146 selected cell populations, were all capable of forming ectopic bone when transplanted subcutaneously into NOD/SCID mice. The findings presented here, describe a multipotential stem cell population within adult human adipose tissue, which appear to be intimately associated with perivascular cells surrounding the blood vessels.