Potential role of activated platelets in homing of human endothelial progenitor cells to subendothelial matrix

Abstract

SummaryEndothelial progenitor cells (EPCs) mobilize from the bone marrow in response to tissue injury and participate in vascular repair. However, there is limited data about the homing mechanisms of EPCs to vascular injury sites. Recently animal experiments indicated that platelets playa role in recruitment of EPCs to injury sites. However, data on the possible interaction between platelets and EPCs within the human system are limited. We, therefore, examined in-vitro human platelet-EPC interaction under static and flow conditions. Human EPCs were isolated from donated buffy coats by magnetic microbeads and flow cytometry cell sorting using CD133 and VEGFR-2, respectively, as markers. Platelets were tested in the form of washed platelets, platelet rich plasma or whole blood. EPCs formed heterotypic aggregates with resting platelets under static conditions, an interaction that was greatly enhanced when platelets were activated by collagen, ADP or thrombin-activation peptide. The platelet-EPC interaction was inhibited by antibodies to P-selectin or P-selectin glycoprotein ligand-1 (PSGL-1), but not by antibodies to glycoproteins Ib-IX-V or IIb/IIIa. When perfused over activated platelets under shear stress of 2.5 dyn/cm2, EPCs tethered to platelayers and either adhered immediately or rolled a short distance before adhering. In addition, platelets promoted the colonization of adherent EPCs in culture conditions. Consistent with recent animal studies, these findings demonstrate that human EPCs interact in vitro with activated platelets under static and flow conditions, mediated through P-selectin–PSGL-1 interaction. This interaction may be a central mechanism for homing of EPCs to vascular injury sites.

Endothelial Progenitor Cells Contribute to the Vascularization of Endometriotic Lesions

“…These mechanisms may include shear stress-induced up-regulation of adhesion molecules of the selectin and integrin family, which have been shown to mediate EPC arrest to the endothelium, 27,28 or capture of EPCs from the bloodstream by activated platelets, which adhere to the wall of ischemically injured microvessels. 29 Circulating EPCs have been markedly increased in the bloodstream after myocardial infarction, bypass surgery, or physical training.…”

Endothelial Progenitor Cells Bind and Inhibit Platelet Function and Thrombus Formation

“…[17][18][19][20] Furthermore, it has been shown that the interaction of platelets with EPCs influences their chemotaxis, adhesion, activation, and differentiation into mature ECs during vascular repair. 17,19,[21][22][23][24] Collectively, these studies suggest the existence of a cross talk between EPCs and platelets in the regulation of each other's function. Received January 14, 2009; accepted September 23, 2009 …”

“…27 In this regard, CD62P has also been involved in the interaction of platelets with EPCs. 17,21,22 Although platelets promote the homing of EPCs at sites of vascular injury and favor their differentiation into ECs, the functional consequences of such interactions on platelets remain unknown. In fact, EPCs secrete many vasoactive and angiogenic factors that may modulate vascular thrombosis and hemostasis.…”

“…25,32 Recently, it has been shown that platelets promote the homing and differentiation of EPCs at sites of vascular injury. [17][18][19][20][21][22][23][24] Conversely, EPCs may influence platelet function and modulate their thrombogenic properties during vascular repair. To analyze and characterize the action of EPCs on platelet function, we first showed that platelets can bind EPCs but to a lower extent than the binding to PBMCs.…”

Assessment of platelet function: Laboratory and point-of-care methods

“…The identification of cellular mediators, tissue specific chemokines, factors and molecular determinants involved in this interactions could be useful to identify new strategies for the vascular repair and tissue regeneration in ischemic organs [159,160] . In this contest, the chemokine CXCL12 (stromal cellderived factor-1α, SDF-1α), principally produced by platelet and stored in α granules, but also released from endothelial cells, is directly involved [161] .…”