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1 Laboratory of Physiology, University of Antwerp, Antwerp, Belgium
2 Haematology - Stem Cell Laboratory, Free University Brussels, Brussels, Belgium
3 HistoGeneX, Edegem, Belgium
* To whom correspondence should be addressed. E-mail: vincentfmsegers{at}yahoo.com.
Objective. Circulating stem cells home within the myocardium, probably as the first step of a tissue regeneration process. This step requires adhesion to cardiac microvascular endothelium (CMVE). In this study, we studied mechanisms of adhesion between CMVE and mesenchymal stem cells (MSCs). Methods. Adhesion was studied in vitro and in vivo. Isolated DiI-labeled rat MSCs were allowed to adhere to cultured CMVE in static and dynamic conditions. Either CMVE or MSCs were pre-treated with cytokines (IL-1
, IL-3, IL-6, SCF, SDF-1 or TNF-
, 10 ng/ml). Control or TNF--treated MSCs were injected intracavitary in rat hearts in vivo. Results. In baseline in vitro conditions, the number of MSCs that adhered to CMVE was highly dependent on the flow rate of the superfusing medium, but remained significant at venous and capillary shear stress amplitudes. Activation of both CMVE and MSCs with TNF- or IL-1 prior to adhesion concentration-dependently increased adhesion of MSCs at each studied level of shear stress. Consistently, in vivo, activation of MSCs with TNF- prior to injection significantly enhanced cardiac homing of MSCs. TNF--induced adhesion could be completely blocked by pre-treating either CMVE or MSCs with anti-VCAM-1 monoclonal antibodies but not by anti-ICAM-1 antibodies. Conclusions. Adhesion of circulating MSCs in the heart appears to be an endothelium-dependent process, and is sensitive to modulation by activators of both MSCs and endothelium. Inflammation and the expression of VCAM-1 but not ICAM-1 on both cell types have a regulatory effect on MSC homing in the heart.
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