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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Submitted May 24, 2006
Accepted July 6, 2006
Mesenchymal stem cells (MSCs) display coordinated rolling
and adhesion behavior on endothelial cells
Brigitte Ruster, Stephan Gottig, Ralf J. Ludwig, Roxana Bistrian, Stefanie Muller, Erhard Seifried, Jens Gille, and Reinhard Henschler*
Institute of Transfusion Medicine and Immune Hematology, Johann-Wolfgang-Goethe University
Department of Dermatology and Venerology, Johann-Wolfgang-Goethe University
Paul-Ehrlich-Institute, Langen
* Corresponding author; email: rhenschler{at}web.de.
To explore the initial steps by which transplanted 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 (PBMC) or
CD34+ hematopoietic progenitors at shear
stresses of up to 2 dynes/cm2. This involved
rapid extension of podia, rolling, and subsequent firm
adhesion which was increased when ECs were pre-stimulated
with TNF-alpha. 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 post-capillary 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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