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-␤, 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.

This study aimed to investigate the biological response to hypoxia as a stimulus, as well as exercise- and vibration-induced shear stress, which is known to induce angiogenesis. Twelve male cyclists (27.8 +/- 5.4 yr) participated in this study. Each subject completed four cycle training sessions under normal conditions (NC) without vibration, NC with vibration, normobaric hypoxic conditions (HC) without vibration, and HC with vibration. Each session lasted 90 min, and sessions were held at weekly intervals in a randomized order. Five blood samples (pretraining and 0 h post-, 0.5 h post-, 1 h post-, and 4 h posttraining) were taken from each subject at each training session. Hypoxia was induced by a normobaric hypoxic chamber with an altitude of 2,500 m. The mechanical forces (cycling with or without vibration) were induced by a cycling ergometer. The parameters VEGF, endostatin, and matrix metalloproteinases (MMPs) were analyzed using the ELISA method. VEGF showed a significant increase immediately after the exercise only with exogenously induced vibrations, as calculated with separate ANOVA analysis. Endostatin increased after training under all conditions. Western blot analysis was performed for the determination of endostatin corresponding to the 22-kDa cleavage product of collagen XVIII. This demonstrated elevated protein content for endostatin at 0 h postexercise. MMP-2 increased in three of the four training conditions. The exception was NC with vibration. MMP-9 reached its maximum level at 4 h postexercise. In conclusion, the results support the contention that mechanical stimuli differentially influence factors involved in the induction of angiogenesis. These findings may contribute to a broader understanding of angiogenesis.

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The enhanced sensitivity of failing human myocardium toward cardiac glycosides may be, at least in part, attributed to a reduced protein expression and activity of the sarcolemmal Na+,K+-ATPase without a change in Na+-Ca2+ exchanger protein expression.