Basic fibroblast growth factor controls migration in human mesenchymal stem cells

Basic fibroblast growth factor controls migration in human mesenchymal stem cells
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DOI:
10.1634/stemcells.2005-0191
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发表时间:
2006-07-01
期刊:
影响因子:
5.2
通讯作者:
Bloch, Wilhelm
Bloch, Wilhelm
中科院分区:
医学2区
文献类型:
--
作者:
Schmidt, Annette;Ladage, Dennis;Bloch, Wilhelm

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间充质干细胞(MSC)的迁移知之甚少。一些治疗方法已经证明,当从不同的应用部位应用时,MSC能够再生损伤的组织。这意味着MSC不仅能够迁移,而且迁移的方向是受控的。参与控制MSC迁移的因素是广泛未知的。在不同条件下检测分离的MSCs的迁移能力。在碱性成纤维细胞生长因子(bFGF)、促红细胞生成素、白细胞介素-6、基质细胞衍生因子-β和血管内皮生长因子存在或不存在的情况下,使用Boyden室测定法检查迁移能力。bFGF尤其能够通过激活Akt/蛋白激酶B(PKB)途径来增加MSC的迁移活性。细胞骨架的取向分析支持了这一结果。在碱性成纤维细胞生长因子梯度的存在下,肌动蛋白丝开发了一个平行的模式,是强烈相关的梯度。令人惊讶的是,bFGF的影响不仅是一个吸引力,但也路由MSC。bFGF梯度实验表明,低浓度的bFGF导致细胞的吸引力,而较高的浓度导致排斥。bFGF的这种矛盾作用为MSC的有目的的路由提供了可能性。
Little is known about the migration of mesenchymal stem cells (MSCs). Some therapeutic approaches had demonstrated that MSCs were able to regenerate injured tissues when applied from different sites of application. This implies that MSCs are not only able to migrate but also that the direction of migration is controlled. Factors that are involved in the control of the migration of MSCs are widely unknown. The migratory ability of isolated MSCs was tested in different conditions. The migratory capability was examined using Boyden chamber assay in the presence or absence of basic fibroblast growth factor (bFGF), erythropoietin, interleukin-6, stromal cell-derived factor-beta, and vascular endothelial growth factor. bFGF in particular was able to increase the migratory activity of MSCs through activation of the Akt/protein kinase B (PKB) pathway. The results were supported by analyzing the orientation of the cytoskeleton. In the presence of a bFGF gradient, the actin filaments developed a parallelized pattern that was strongly related to the gradient. Surprisingly, the influence of bFGF was not only an attraction but also routing of MSCs. The bFGF gradient experiment showed that low concentrations of bFGF lead to an attraction of the cells, whereas higher concentrations resulted in repulsion. This ambivalent effect of bFGF provides the possibility to a purposeful routing of MSCs.