Abstract
Background aims. Intravenously applied mesenchymal stromal cells (MSC) are under investigation for numerous clinical indications. However, their capacity to activate shear stress-dependent adhesion to endothelial ligands is incompletely characterized. Methods. Parallel-plate flow chambers were used to induce firm adhesion of MSC to integrin ligand vascular cell adhesion molecule (VCAM)-1. Human MSC were stimulated by chemokine (C-C motif) ligand (CCL15)/macrophage inflammatory protein (MIP-5), CCL19/MIP-3β chemokine (C-X-C motif) ligand (CXCL8)/interleukin (IL)-8, CXCL12/ stromal derived factor (SDF-1) or CXCL13/B lymphocyte chemoattractant (BLC). Results. Two MSC isolates responded to three chemokines (either to CCL15, CCL19 and CXCL13, or to CCL19, CXCL12 and CXCL13), two isolates responded to two chemokines (to CCL15 and CCL19, or to CCL19 and CXCL13), and one isolate responded to CCL19 only. In contrast, all tested MSC isolates responded to selectins (P-selectin and E-selectin) or integrin ligand VCAM-1, as visualized by a velocity reduction under flow. Conclusions. Inter-individual variability of chemokine-induced integrin activation should be considered when evaluating human MSC as cellular therapies.
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Acknowledgments
Work reported in this paper has been supported by research grants from the Bundesministerium für Bildung und Forschung (grants 01GN0952 and 05GN0525, to R.H.), EU 7th Framework Programme CASCADE (grant 223236 to R.H.) and Deutsche Forschungsgemeinschaft Excellence Cluster Cardio-Pulmonary System (to E.S. and R.H.).
Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the paper.