Junctional Adhesion Molecule A Expressed on Human CD34 ⁺ Cells Promotes Adhesion on Vascular Wall and Differentiation Into Endothelial Progenitor Cells

Abstract

ϩ cells isolated from human peripheral blood can differentiate into endothelial cells, contributing to neoangiogenesis. Since then, numerous experimental studies 2-5 investigated and further supported the role of CD34 ϩ stem cells in vascular regeneration and tissue healing. The mobilization of CD34 ϩ cells expressing early cardiac, muscle, and endothelial markers into peripheral blood was reported in patients with acute myocardial infarction. After tissue ischemia, progenitor cells are mobilized from their bone marrow or peripheral niches into circulation, adhere at sites of the vascular lesion, and differentiate into a variety of mature cell types according to their origin and the local environment. 6,7 Impairment in this pathophysiological process, as the result of either low numbers of circulating progenitor cells or dysfunctional progenitor cells, leads to inadequate vascular repair; on coexistence with different cardiovascular risk factors, this type of impairment leads to vascular injury and atherosclerosis. The level of circulating CD34 ϩ progenitor cells predicts the occurrence of cardiovascular events and death from cardiovascular causes and correlates with cardiovascular risk factors in patients with coronary artery disease. 8 Therefore, it is not surprising that a plethora of in vivo studies and clinical trials were raised to examine the therapeutic benefits of CD34 ϩ cell transplantation in ischemic disease. ϩ progenitor cells into bone marrow has been extensively studied, 11 domiciliation of CD34 ϩ precursor cells into peripheral tissues and differentiation into endothelial cells is poorly understood. The role of platelets in domiciliation and subsequent differentiation of progenitor cells has been recently highlighted. 12-17 Adherent platelets secrete a potent stem cell chemokine, the stromal cell-derived factor 1 (SDF-1); recruit circulating progenitor cells; and induce differentiation of the latter into endothelial cells. 13,15 To our knowledge, the mechanisms responsible for platelet-mediated recruitment and differentiation of CD34 ϩ cells have not been sufficiently elucidated.Junctional adhesion molecule A (JAM-A; also known as JAM-1 or F11 receptor) is a cell adhesion molecule expressed on a variety of cells, including platelets playing a crucial role in platelet adhesion and vascular inflammation. 18 The role of platelet-derived JAM-A in adhesion and differentiation of human CD34ϩ cells has not been described. The present study analyzes the role of JAM-A in the adhesion and differentiation of CD34 ϩ cells into endothelial progenitor cells. MethodsA detailed "Methods" section is given in the Supplemental Material (available online at http://atvb.ahajournals.org). Isolation and Culture of Platelets, Human CD34 ؉ Cells, and Human Arterial Endothelial CellsHuman platelets were isolated as previously described. 13,15 Human CD34 ϩ cells were isolated from either human cord blood or bone marrow and cultured as previously described. 14,15 Human arterial endothelial cells (haECs) were isolated and pa...

Engagement of αIIbβ3 (GPIIb/IIIa) with ανβ3 Integrin Mediates Interaction of Melanoma Cells with Platelets

“…Next, we monitored adhesion of circulating B16 melanoma cells to platelets under more physiological conditions in vivo using intravital microscopy. In the applied model, platelet accumulation at the vascular wall was provoked by ischemia-reperfusion injury induced by transient ligation of the mesenteric artery (26), and thus, plateletmelanoma cell interaction could be studied in vivo. Subsequently, fluorescently labeled B16 melanoma cells were injected into the jugular vein of syngeneic C57BL/6J mice after platelet depletion or control treatment.…”

“…Human platelets were isolated as described previously (25)(26)(27). Briefly, venous blood was drawn from the antecubital vein of healthy volunteers and collected in acid/citrate/dextrose buffer.…”

“…Intravital microscopy and induction of platelet accumulation to study platelet-melanoma cell interaction in vivo were performed principally as described before (26). Wild-type C57BL/6J mice (Charles River Laboratories) were anesthetized by intraperitoneal injection of a solution of midazolam (5 mg/kg body weight; Ratiopharm), medetomidine (0.5 mg/kg body weight; Pfizer), and fentanyl (0.05 mg/kg body weight, CuraMed Pharma GmbH).…”

Progesterone Increases Circulating Endothelial Progenitor Cells and Induces Neural Regeneration after Traumatic Brain Injury in Aged Rats

“…EPCs or CD34 positive/CD133 positive cells have been demonstrated to repair the denuded vessel walls and to promote renewal of endothelium (Rufaihah et al, 2010;Senegaglia et al, 2010;Walter et al, 2002). CD34 positive cells play an indispensable role in angiogenesis (Al-Jarrah et al, 2010;Stellos et al, 2010;Wang et al, 2010). CD34 positive cells selectively home to the sites of angiogenesis, integrate into the microvascular endothelium, and differentiate into mature endothelial cells (Krupinski et al, 2003;Morris et al, 2003).…”

Junctional Adhesion Molecules (JAMs) - New Players in Breast Cancer?

“…In support of a potential association between high JAM-A and poor differentiation status, high JAM-A gene or protein expression has been associated with a poorer grade of differentiation in tissues from patients with invasive breast cancer (McSherry et al, 2009). Conversely, JAM-A has been found to mediate the differentiation of CD34+ progenitor cells to endothelial progenitor cells and to facilitate CD34+ cell-induced re-endothelialization in vitro (Stellos et al, 2010). This suggests that JAM-A is required for circulating CD34+ progenitor cells to recognise a site of injury, differentiate into endothelial cells and proliferate to repair the injured endothelium.…”