title: Platelet derived bFGF mediates vascular integrative mechanisms of mesenchymal stem cells in vitro.
abstract: 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.
authors.affiliation: Medizinische Klinik III, Department of Cardiovascular Medicine, Eberhard Karls Universität Tübingen, Germany. harald.langer@med.uni-tuebingen.de
authors.forename: Harald F
authors.initials: HF
authors.lastname: Langer
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Stellos
authors.forename: Caroline
authors.initials: C
authors.lastname: Steingen
authors.forename: Amrei
authors.initials: A
authors.lastname: Froihofer
authors.forename: Tanja
authors.initials: T
authors.lastname: Schönberger
authors.forename: Björn
authors.initials: B
authors.lastname: Krämer
authors.forename: Boris
authors.initials: B
authors.lastname: Bigalke
authors.forename: Andreas E
authors.initials: AE
authors.lastname: May
authors.forename: Peter
authors.initials: P
authors.lastname: Seizer
authors.forename: Iris
authors.initials: I
authors.lastname: Müller
authors.forename: Friederike
authors.initials: F
authors.lastname: Gieseke
authors.forename: Dorothea
authors.initials: D
authors.lastname: Siegel-Axel
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
authors.forename: Annette
authors.initials: A
authors.lastname: Schmidt
authors.forename: Hans P
authors.initials: HP
authors.lastname: Wendel
authors.forename: Ingo
authors.initials: I
authors.lastname: Müller
authors.forename: Wilhelm
authors.initials: W
authors.lastname: Bloch
authors.forename: Meinrad
authors.initials: M
authors.lastname: Gawaz