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Platelets secrete stromal cell–derived factor 1 and recruit bone marrow–derived progenitor cells to arterial thrombi in vivo

¹ Deutsches Herzzentrum and Medizinische Klinik, Technical University of Munich, D-80636 Munich, Germany
² Institute for Medical Microbiology, Immunology, and Hygiene, ³ Clinical Cooperation Group Vaccinology, National Research Center for Environment and Health (GSF), and ⁴ Institute of Pathology, Klinikum rechts der Isar, Technical University of Munich, D-81675 Munich, Germany
⁵ Procorde GmbH, D-82152 Martinsried, Germany
⁶ Institut für Prophylaxe und Epidemiologie der Kreislaufkrankheiten, LMU München, D-80336 Munich, Germany
⁷ Max-Planck Institute of Molecular Biomedicine, University of Münster, D-48149 Münster, Germany
⁸ Harvard Medical School, Children's Hospital, Boston, MA 02115
⁹ Institute for Biomedical Research, Birmingham University Medical School, Birmingham B15 2TT, England, UK
¹⁰ Innere Medizin III, Universität Tübingen, D-72076 Tübingen, Germany

CORRESPONDENCE Steffen Massberg: massberg{at}cbr.med.harvard.edu

The accumulation of smooth muscle and endothelial cells is essential for remodeling and repair of injured blood vessel walls. Bone marrow–derived progenitor cells have been implicated in vascular repair and remodeling; however, the mechanisms underlying their recruitment to the site of injury remain elusive. Here, using real-time in vivo fluorescence microscopy, we show that platelets provide the critical signal that recruits CD34⁺ bone marrow cells and c-Kit⁺ Sca-1⁺ Lin^– bone marrow–derived progenitor cells to sites of vascular injury. Correspondingly, specific inhibition of platelet adhesion virtually abrogated the accumulation of both CD34⁺ and c-Kit⁺ Sca-1⁺ Lin^– bone marrow–derived progenitor cells at sites of endothelial disruption. Binding of bone marrow cells to platelets involves both P-selectin and GPIIb integrin on platelets. Unexpectedly, we found that activated platelets secrete the chemokine SDF-1, thereby supporting further primary adhesion and migration of progenitor cells. These findings establish the platelet as a major player in the initiation of vascular remodeling, a process of fundamental importance for vascular repair and pathological remodeling after vascular injury.

Abbreviations used: BM-PC, BM-derived PC; DCF, dichlorofluorescein; EC, endothelial cell; IVM, intravital video fluorescence microscopy; KSL, c-Kit⁺ Sca-1⁺ Lin^–; PC, progenitor cell; PSGL, P-selectin glycoprotein ligand; SDF-1, stromal cell–derived factor 1; SMC, smooth muscle cell.

S. Massberg's present address is CBR Institute for Biomedical Research and Department of Pathology, Harvard Medical School, Boston, MA 02115.

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