on April 20, 2006
Published online before print April 20, 2006, doi: 10.1161/01.ATV.0000222982.55731.f1
| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Submitted on October 12, 2005
Accepted on March 31, 2006
Fibrin and Activated Platelets Cooperatively Guide Stem Cells to a Vascular Injury and Promote Differentiation Towards an Endothelial Cell Phenotype
H. C. de Boer *;
From the Department of Nephrology (H.C.d.B., C.V., T.J.R., A.J.v.Z.), Leiden University Medical Center, Leiden, The Netherlands; Department of Pulmonary Diseases (L.H.U.), University Medical Center Utrecht, The Netherlands; Departments of Experimental Immunohaematology and Immunohaematology-Bloodtransfusion (J.J.Z.), Sanquin Research, Amsterdam and Leiden University Medical Center, Leiden, The Netherlands; Division of Biopharmaceutics (I.B., E.A.B.), Leiden/Amsterdam Center for Drug Research, Gorleaus Laboratories, Leiden University, The Netherlands.
* To whom correspondence should be addressed. E-mail: h.c.deboer{at}lumc.nl.
Objective--Bone marrow-derived progenitor cells play a role in vascular regeneration. However, their homing to areas of vascular injury is poorly understood. One of the earliest responses to an injury is the activation of coagulation and platelets. In this study we assessed the role of hemostatic components in the recruitment of CD34+ cells to sites of injury.
Methods and Results--Using an ex vivo injury model, representing endothelial cell (EC) injury or vessel denudation, we studied homing of CD34+ under flow. Platelet aggregates facilitated initial tethering and rolling of CD34+ cells through interaction of P-selectin expressed by platelets and P-selectin glycoprotein ligand-1 (PSGL-1), expressed by CD34+ cells. Ligation of PSGL-1 activated adhesion molecules on CD34+ cells, ultimately leading to firm adhesion of CD34+ cells to tissue factor-expressing ECs or to fibrin-containing thrombi formed on subendothelium. We also demonstrate that fibrin-containing thrombi can support migration of CD34+ cells to the site of injury and subsequent differentiation toward a mature EC phenotype. Additionally, intravenously injected CD34+ cells homed in vivo to denuded arteries in the presence of endogenous leukocytes.
Conclusions--We provide evidence that hemostatic factors, associated with vascular injury, provide a regulatory microenvironment for re-endothelialization mediated by circulating progenitor cells.
This article has been cited by other articles:
 |
|
 |
|
  M. Prokopi, G. Pula, U. Mayr, C. Devue, J. Gallagher, Q. Xiao, C. M. Boulanger, N. Westwood, C. Urbich, J. Willeit, et al. Proteomic analysis reveals presence of platelet microparticles in endothelial progenitor cell cultures Blood, July 16, 2009; 114(3): 723 - 732. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 F. A. Bozza, A. M. Shah, A. S. Weyrich, and G. A. Zimmerman Amicus or Adversary: Platelets in Lung Biology, Acute Injury, and Inflammation Am. J. Respir. Cell Mol. Biol., February 1, 2009; 40(2): 123 - 134. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. R. Schroeter, M. Leifheit, P. Sudholt, N.-M. Heida, C. Dellas, I. Rohm, F. Alves, M. Zientkowska, S. Rafail, M. Puls, et al. Leptin Enhances the Recruitment of Endothelial Progenitor Cells Into Neointimal Lesions After Vascular Injury by Promoting Integrin-Mediated Adhesion Circ. Res., August 29, 2008; 103(5): 536 - 544. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Q. Xu Stem Cells and Transplant Arteriosclerosis Circ. Res., May 9, 2008; 102(9): 1011 - 1024. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. E. May, P. Seizer, and M. Gawaz Platelets: Inflammatory Firebugs of Vascular Walls Arterioscler Thromb Vasc Biol, March 1, 2008; 28(3): s5 - s10. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. C. Rafii, B. Psaila, J. Butler, D. K. Jin, and D. Lyden Regulation of Vasculogenesis by Platelet-Mediated Recruitment of Bone Marrow-Derived Cells Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 217 - 222. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. B. Rookmaaker, M. C. Verhaar, H. C. de Boer, R. Goldschmeding, J. A. Joles, H. A. Koomans, H.-J. Grone, and T. J. Rabelink Met-RANTES reduces endothelial progenitor cell homing to activated (glomerular) endothelium in vitro and in vivo Am J Physiol Renal Physiol, August 1, 2007; 293(2): F624 - F630. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. T. Nurden Platelets and Tissue Remodeling: Extending the Role of the Blood Clotting System Endocrinology, July 1, 2007; 148(7): 3053 - 3055. [Full Text] [PDF]
|
|
|
|
|
|
M. Hristov, A. Zernecke, K. Bidzhekov, E. A. Liehn, E. Shagdarsuren, A. Ludwig, and C. Weber Importance of CXC Chemokine Receptor 2 in the Homing of Human Peripheral Blood Endothelial Progenitor Cells to Sites of Arterial Injury Circ. Res., March 2, 2007; 100(4): 590 - 597. [Abstract] [Full Text] [PDF]
|
|