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

Abstract

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-1α, 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.

Transforming Growth Factor-β Promotes Recruitment of Bone Marrow Cells and Bone Marrow-derived Mesenchymal Stem Cells through Stimulation of MCP-1 Production in Vascular Smooth Muscle Cells

“…The contribution of BMPC to the neointimal lesion has been well described (3)(4)(5)33), however, characterization of the progenitor cells is still controversial. Initial studies suggested that hematopoietic stem cells (HSC) may differentiate into SMC or endothelial cells; however, later studies have suggested that transdifferentiation of HSC into non-hematopoietic cells is a rare event (6, 36 -39).…”

“…These "activated" VSMC migrate to the subintima space where they continue to proliferate and, thus, form the neointimal lesion (2). Recent evidence, however, suggests that bone marrow-derived progenitor cells (BMPC) are recruited to sites of vascular injury and may also play an essential role in the development of intimal hyperplasia (3)(4)(5)(6)(7).…”

“…The following three steps are believed to occur with BMPC in response to arterial injury; 1) mobilization of cells from the bone marrow, 2) recruitment of these cells to the site of injury, and 3) differentiation of progenitor cells into cells of the arterial wall (8). A number of chemokines are responsible for the second phase of this process, and proteins that have been implicated include but are not limited to stromal-derived factor-1␣ (SDF-1␣) (3,4), c-kit (5), and monocyte chemoattractant protein 3 (MCP-3) (9, 10). We and others have recently found that some of these chemoattractants can be released by VSMC at the time of arterial injury, although the signals that stimulate their release have not been elucidated.…”

Therapeutic Treatment with Sustained-Release Platelet-Rich Plasma Restores Blood Perfusion by Augmenting Ischemia-Induced Angiogenesis and Arteriogenesis in Diabetic Mice

“…Our data reflects that PRP contains a small amount of VEGF and a relatively large amount of SDF-1α. Massberg et al [38] suggested that platelets secrete SDF-1α and recruit bone marrow-derived progenitor cells to the injured arterial site. Our previous study also showed that the sustained release of PRP accelerates the homing of hematopoietic progenitor cells to the ischemic site in vivo which reflects the contribution of the sustained release of PRP to vasculogenesis in hind limb ischemia [11].…”

Platelets as a Novel Source of Pro-Inflammatory Chemokine CXCL14

“…Upon activation platelets release macrophage-migration inhibition factor (MIF) or stromal cell-derived factor-1 (SDF-1/CXCL12) [5, 22], engage a wide range of chemokine receptors like CXCR2, CXCR4, CXCR7 to impose both autocrine and paracrine effects on interacting cells in the platelet micro-environment [23]. Platelet-derived CXCL12 is a chemokine, which acts as a regulator of monocyte adhesion, survival, and migration of monocytes through its receptors CXCR4 and CXCR7 [4].…”