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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:217.)
© 2008 American Heart Association, Inc.

Brief Review

Regulation of Vasculogenesis by Platelet-Mediated Recruitment of Bone Marrow–Derived Cells

Daniel C. Rafii; Bethan Psaila; Jason Butler; David K. Jin; David Lyden

From the Departments of Pediatrics and Cell Biology (D.C.R., B.P., D.L.), and the Department of Genetic Medicine (J.B.D.K.J.), Weill Cornell Medical College and Memorial Sloan-Kettering Cancer Center, New York, NY.

Correspondence to David C Lyden, MD, PhD, Weill Cornell Medical College, Department of Pediatrics, Director of Cellular Oncology, New York, NY, 10021. E-mail dcl2001{at}med.cornell.edu

Series Editor: Stefanie Dimmeler
Novel Mediators and Mechanisms in Angiogenesis and Vasculogenesis
ATVB In Focus

Previous Brief Reviews in this Series:

•Dimmeler S. Novel mediators and mechanisms in angiogenesis and vasculogenesis. Arterioscler Thromb Vasc Biol. 2005;25:2245.
•Ferguson JE, Kelley RW, Patterson C. Mechanisms of endothelial differentiation in embryonic vasculogenesis. Arterioscler Thromb Vasc Biol. 2005;25:2246–2254.
•Werner N, Nickenig G. Influence of cardiovascular risk factors on endothelial progenitor cells: limitations for therapy? Arterioscler Thromb Vasc Biol. 2006;26:257–266.
•van Hinsbergh VWM, Engelse MA, Quax PHA. Pericellular proteases in angiogenesis and vasculogenesis. Arterioscler Thromb Vasc Biol. 2006;26:716–728.
•Sata M. Role of circulating vascular progenitors in angiogenesis, vascular healing, and pulmonary hypertension: lessons from animal models. Arterioscler Thromb Vasc Biol. 2006;26:1008–1014.
•Dimmeler S, Burchfield J, Zeiher AM. Cell-based therapy of myocardial infarction. Arterioscler Thromb Vasc Biol. 2008;28:208–216.

Bone marrow–derived cells contribute to physiological and pathological vascular remodeling throughout ontogenesis and adult life. During tissue regeneration and tumor growth, the release of cytokines and chemokines mediates the recruitment of hematopoietic and endothelial progenitor cells that contribute to the assembly of neovessels. Current evidence implies that platelets contribute structurally and instructively to vascular remodeling. Platelets adhere almost immediately to exposed or activated endothelium, and they are major storage and delivery vehicles for pro- and antiangiogenic growth factors including VEGF-A and thrombospondin (TSP), and cytokines and chemokines, such as stromal-derived factor 1 (SDF-1). By site-specific deployment of these factors, platelets orchestrate the local angiogenic stimulus within a tissue and direct the recruitment and differentiation of circulating bone marrow–derived cells. These insights have profound clinical implications; inhibition of platelet-deployed growth factors or their receptors may be an effective strategy to block tumor growth, whereas activation of these pathways may be used to accelerate revascularization and tissue regeneration.

Platelets are major delivery vehicles for pro- and antiangiogenic growth factors. During the formation of new blood vessels, platelet-deployed factors support the recruitment and differentiation of bone marrow–derived cells. Therapeutic manipulation of the site-specific deployment of these factors by platelets may be used to inhibit tumor growth or promote tissue restoration.

Key Words: angiogenesis • hematopoietic progenitor cells • endothelial progenitor cells • ischemia • platelets

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