Langer Harald F, Stellos Konstantinos, Steingen Caroline, Froihofer Amrei, Schönberger Tanja, Krämer Björn, Bigalke Boris, May Andreas E, Seizer Peter, Müller Iris, Gieseke Friederike, Siegel-Axel Dorothea, Meuth Sven G, Schmidt Annette, Wendel Hans P, Müller Ingo, Bloch Wilhelm, Gawaz Meinrad
Medizinische Klinik III, Department of Cardiovascular Medicine, Eberhard Karls Universität Tübingen, Germany.
J Mol Cell Cardiol. 2009 Aug;47(2):315-25. doi: 10.1016/j.yjmcc.2009.03.011. Epub 2009 Mar 27.
Patients with myocardial infarction reveal an altered number of circulating mesenchymal stem cells (MSCs). Recently, it was shown that MSCs are able to regenerate myocardial tissue and to differentiate into endothelial cells. The homing mechanisms of MSCs from the circulation into the target tissue, however, are not understood so far. In this study, we evaluated the impact of platelets on MSC recruitment, proliferation, migration and integration into the endothelium. MSCs expressing alpha(v)beta(3) integrin were recruited to human arterial endothelial cells exposed to isolated platelets or IL-1 beta under high shear conditions. Furthermore, induction of vascular injury in vivo resulted in increased recruitment of injected MSCs as assessed by intravital microscopy and depletion of platelets significantly reduced this adhesion. The interaction of platelets and MSCs was inhibited by pre-incubation with the mAb 7E3 or an RGD protein both blocking beta(3) integrin mediated adhesion. Platelets had a chemotactic effect on MSCs, promoted a migratory MSC phenotype and dose- and activation-dependently enhanced migration of MSCs, a process, which was mediated by basic fibroblast growth factor (bFGF). Similarly, platelet derived bFGF increased proliferation of MSCs. Coincubation of MSCs with platelets facilitated integration into an endothelial monolayer, which was significantly reduced by pre-incubation with a blocking mAb to bFGF. We conclude that platelets may play a critical part in the recruitment of MSCs to the endothelium, influence MSC function and promote integration of MSCs into the endothelium.
心肌梗死患者体内循环间充质干细胞（MSC）数量会发生改变。最近研究表明，MSC能够再生心肌组织并分化为内皮细胞。然而，目前尚不清楚MSC从循环系统归巢至靶组织的机制。在本研究中，我们评估了血小板对MSC募集、增殖、迁移以及向内皮细胞整合的影响。在高剪切条件下，表达α(v)β(3)整合素的MSC被募集至暴露于分离血小板或IL-1β的人动脉内皮细胞。此外，通过活体显微镜评估发现，体内血管损伤诱导导致注射的MSC募集增加，而血小板耗竭则显著降低这种黏附。用单克隆抗体7E3或RGD蛋白预孵育均可抑制血小板与MSC的相互作用，二者均能阻断β(3)整合素介导的黏附。血小板对MSC具有趋化作用，促进MSC迁移表型，且剂量和激活依赖性地增强MSC迁移，这一过程由碱性成纤维细胞生长因子（bFGF）介导。同样，血小板衍生的bFGF可增加MSC的增殖。MSC与血小板共孵育有助于其整合入内皮单层，而用bFGF阻断单克隆抗体预孵育可显著降低这种整合。我们得出结论，血小板可能在将MSC募集至内皮细胞过程中起关键作用，影响MSC功能并促进MSC向内皮细胞的整合。
