Autocrine fibroblast growth factor 2 increases the multipotentiality of human adipose-derived mesenchymal stem cells
Autocrine fibroblast growth factor 2 increases the multipotentiality of human adipose-derived mesenchymal stem cells
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DOI：
10.1634/stemcells.2007-0480
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发表时间：
2008-06-01
期刊：
影响因子：
5.2
通讯作者：
Cool, Simon M.
中科院分区：
文献类型：
--
作者：
Rider, David A.;Dombrowski, Christian;Cool, Simon M.
多能间充质干细胞（MSCs）首先在骨髓中被发现，随后在许多其他组织中被发现，包括脂肪、软骨、肌肉和骨骼。脂肪组织已被确定为骨髓的替代品，作为分离间充质干细胞的来源，因为它既不受体积限制，也不具有采收的侵入性。本研究比较了来自12个年龄和性别匹配供体的骨髓间充质干细胞（BMSCs）和脂肪间充质干细胞（AMSCs）的多能性。在表型上，这些细胞非常相似，只有三种表面标记，CD106， CD146和HLA-ABC，在骨髓间质干细胞中差异表达。尽管BMSCs中的集落形成单位-成纤维细胞数量高于AMSCs，但多种干细胞相关基因的表达，如成纤维细胞生长因子2 （FGF2）、Wnt通路效应物FRAT1和frzzled1以及其他自我更新标志物，在AMSCs中更高。此外，AMSCs显示出增强的成骨和成脂潜能，而BMSCs比AMSCs更容易形成软骨细胞。然而，通过从实验中去除增殖的影响，AMSCs在成骨和成脂分化的能力上不再优于BMSCs。抑制FGF2/成纤维细胞生长因子受体1信号通路表明，AMSCs和BMSCs的增殖都需要FGF2，但阻断FGF2信号通路对成骨分化没有直接影响。
Multipotent mesenchymal stem cells (MSCs), first identified in the bone marrow, have subsequently been found in many other tissues, including fat, cartilage, muscle, and bone. Adipose tissue has been identified as an alternative to bone marrow as a source for the isolation of MSCs, as it is neither limited in volume nor as invasive in the harvesting. This study compares the multipotentiality of bone marrow-derived mesenchymal stem cells (BMSCs) with that of adipose-derived mesenchymal stem cells (AMSCs) from 12 age- and sex-matched donors. Phenotypically, the cells are very similar, with only three surface markers, CD106, CD146, and HLA-ABC, differentially expressed in the BMSCs. Although colony-forming units-fibroblastic numbers in BMSCs were higher than in AMSCs, the expression of multiple stem cell-related genes, like that of fibroblast growth factor 2 (FGF2), the Wnt pathway effectors FRAT1 and frizzled 1, and other self-renewal markers, was greater in AMSCs. Furthermore, AMSCs displayed enhanced osteogenic and adipogenic potential, whereas BMSCs formed chondrocytes more readily than AMSCs. However, by removing the effects of proliferation from the experiment, AMSCs no longer out-performed BMSCs in their ability to undergo osteogenic and adipogenic differentiation. Inhibition of the FGF2/fibroblast growth factor receptor 1 signaling pathway demonstrated that FGF2 is required for the proliferation of both AMSCs and BMSCs, yet blocking FGF2 signaling had no direct effect on osteogenic differentiation.