Institute of Transfusion Medicine and Immune Hematology, German Red Cross Blood Donor Service Baden-Württemberg - Hessen, Clinics of the Goethe University, Frankfurt, Germany.
Cytotherapy. 2011 Nov;13(10):1172-9. doi: 10.3109/14653249.2011.602339. Epub 2011 Aug 26.
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.
静脉内应用的间充质基质细胞(MSC)正在被研究用于多种临床适应证。然而,其激活与剪切力相关的黏附到内皮配体的能力尚未完全确定。方法:使用平行平板流动室来诱导 MSC 与整合素配体血管细胞黏附分子(VCAM)-1 的牢固黏附。通过趋化因子(C-C 基序)配体(CCL15)/巨噬细胞炎性蛋白(MIP-5)、CCL19/MIP-3β 趋化因子(C-X-C 基序)配体(CXCL8)/白细胞介素(IL)-8、CXCL12/基质衍生因子(SDF-1)或 CXCL13/B 淋巴细胞趋化因子(BLC)刺激人 MSC。结果:两种 MSC 分离物对三种趋化因子(CCL15、CCL19 和 CXCL13,或 CCL19、CXCL12 和 CXCL13)中的任一种有反应,两种分离物对两种趋化因子(CCL15 和 CCL19,或 CCL19 和 CXCL13)有反应,而一种分离物仅对 CCL19 有反应。相比之下,所有测试的 MSC 分离物都对选择素(P 选择素和 E 选择素)或整合素配体 VCAM-1 有反应,这可以通过在流动下的速度降低来观察到。结论:在评估作为细胞疗法的人 MSC 时,应该考虑趋化因子诱导的整合素激活的个体间变异性。