Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells

To explore the initial steps by which transplanted mesenchymal stem cells (MSCs) interact with the vessel wall in the course of extravasation, we studied binding of human MSCs to endothelial cells (ECs). In a parallel plate flow chamber, MSCs bound to human umbilical vein ECs (HUVECs) similar to per...

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Bibliographic Details
Published in:Blood 2006-12, Vol.108 (12), p.3938-3944
Main Authors: Rüster, Brigitte, Göttig, Stephan, Ludwig, Ralf J., Bistrian, Roxana, Müller, Stefanie, Seifried, Erhard, Gille, Jens, Henschler, Reinhard
Format: Article
Language:English
Subjects:
Animals
Antigens, CD34
Cell Adhesion
Cell Adhesion Molecules - biosynthesis
Cell Movement
Endothelial Cells - cytology
Endothelial Cells - metabolism
Female
Humans
Male
Mesenchymal Stem Cells - cytology
Mesenchymal Stem Cells - metabolism
Mice
Microscopy, Video
Stress, Mechanical
Umbilical Veins - cytology
Umbilical Veins - metabolism
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Summary:To explore the initial steps by which transplanted mesenchymal stem cells (MSCs) interact with the vessel wall in the course of extravasation, we studied binding of human MSCs to endothelial cells (ECs). In a parallel plate flow chamber, MSCs bound to human umbilical vein ECs (HUVECs) similar to peripheral-blood mononuclear cells (PBMCs) or CD34+ hematopoietic progenitors at shear stresses of up to 2 dynes/cm2. This involved rapid extension of podia, rolling, and subsequent firm adhesion that was increased when ECs were prestimulated with TNF-α. MSC binding was suppressed when ECs were pretreated with function-blocking anti–P-selectin antibody, and rolling of MSCs was induced on immobilized P-selectin, indicating that P-selectin was involved in this process. Preincubation of HUVECs with anti–VCAM-1 or of MSCs with anti–VLA-4 antibodies suppressed binding of MSCs to HUVECs but did not enhance inhibition by anti–P-selectin, indicating that both P-selectin and VCAM-1 are equally required for this process. Intravital microscopy demonstrated the capacity of MSCs to roll and adhere to postcapillary venules in vivo in a mouse model in a P-selectin–dependent manner. Thus, MSCs interact in a coordinated fashion with ECs under shear flow, engaging P-selectin and VCAM-1/VLA-4.
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2006-05-025098