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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3938-3944.
Prepublished online as a Blood First Edition Paper on August 8, 2006; DOI 10.1182/blood-2006-05-025098.
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TRANSPLANTATION
Mesenchymal stem cells display coordinated rolling and adhesion behavior on endothelial cells
Brigitte Rüster,
Stephan Göttig,
Ralf J. Ludwig,
Roxana Bistrian,
Stefanie Müller,
Erhard Seifried,
Jens Gille, and
Reinhard Henschler
From the Stem Cell Biology Group, DRK Institute of Transfusion Medicine and Immune Hematology, and Department of Dermatology and Venerology, Johann-Wolfgang-Goethe University, Frankfurt am Main; and Paul-Ehrlich Institute, Langen, Germany.
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- . 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.
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