Schmidt Annette, Ladage Dennis, Schinköthe Timo, Klausmann Ursula, Ulrichs Christoph, Klinz Franz-Josef, Brixius Klara, Arnhold Stefan, Desai Biren, Mehlhorn Uwe, Schwinger Robert H G, Staib Peter, Addicks Klaus, Bloch Wilhelm
Department of Molecular and Cellular Sport Medicine, German Sport University Cologne.
Stem Cells. 2006 Jul;24(7):1750-8. doi: 10.1634/stemcells.2005-0191.
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.
关于间充质干细胞(MSC)的迁移,人们了解甚少。一些治疗方法已表明,当从不同应用部位应用时,MSC能够再生受损组织。这意味着MSC不仅能够迁移,而且迁移方向是可控的。参与控制MSC迁移的因素目前还知之甚少。在不同条件下测试了分离的MSC的迁移能力。在存在或不存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的情况下,使用博伊登室试验检测迁移能力。特别是bFGF能够通过激活Akt/蛋白激酶B(PKB)途径来增加MSC的迁移活性。通过分析细胞骨架的方向,这些结果得到了支持。在存在bFGF梯度的情况下,肌动蛋白丝形成了与梯度密切相关的平行模式。令人惊讶的是,bFGF的影响不仅是吸引,还包括引导MSC的迁移方向。bFGF梯度实验表明,低浓度的bFGF会导致细胞被吸引,而高浓度则会导致排斥。bFGF的这种矛盾效应为有目的地引导MSC迁移提供了可能性。