The regulation of plasmin generation on cell surfaces is of critical importance in the control of vascular homeostasis. Cellderived microparticles participate in the dissemination of biological activities. However, their capacity to promote plasmin generation has not been documented. In this study, we show that endothelial microparticles (EMPs) from tumor necrosis factor ␣ (TNF␣) - IntroductionMicroparticles (MPs) are vesicles resulting from the blebbing of the cellular membrane of most activated or apoptotic cells. 1 These microvesicles have been described in various cellular models and in different pathological conditions as reliable hallmarks of cell damage. 2 Because they convey various bioactive effectors originating from the parent cells, MPs may exhibit a spectrum of biological activities: they regulate endothelial or blood cell functions, participate in inflammatory responses or angiogenesis, and propagate biological responses involved in hemostatic balance. 3 We previously reported the capacity of endothelial cells to release microparticles after inflammatory stimulation and the presence of increased levels of circulating endothelial microparticles (EMPs) in patients with thrombotic disorders. 4 Since this initial report, elevated levels of EMPs have been documented in various pathological conditions including coronary syndromes, 5 renal failure, 6 diabetes, 7 antiphospholipid syndrome, 8 thrombotic thrombocytopenic purpura, 9 and sickle cell disease, 10 in which they reflect endothelial dysfunction and are associated with a poor clinical outcome.EMPs provide procoagulant phospholipid surfaces for the assembly and activation of coagulation factors, mainly through phosphatidylserine translocation to the exoplasmic leaflet as a result of membrane remodeling. Their involvement in thrombin generation also results from their capacity to harbor, deliver, or induce tissue factor activity. 11-13 However, a more complex contribution to the hemostatic balance is suggested by their expression of thrombomodulin, tissue factor pathway inhibitor, and endothelial protein C receptor, thus providing a possible antithrombotic counterbalance. 14,15 Another key regulator of the vascular homeostasis is the plasminogen activation system. Plasminogen activation is mediated by 2 serine proteases: tissue-type plasminogen activator (tPA), which is mainly implicated in fibrinolysis, and urokinase-type plasminogen activator (uPA), which is critically involved in pericellular proteolysis due to its high affinity cell-surface receptor uPAR. 16 Plasmin generation induced by uPA and subsequent activation of matrix metalloproteinases (MMPs) promote cell migration through interstitial matrix and participate in processes such as tissue remodeling, cancer invasion, and angiogenesis. [17][18][19] Importantly, we have shown that uncontrolled plasminogen activation can have deleterious consequences by inducing cell detachment and apoptosis. 20,21 The regulation of plasmin generation at the endothelial surface is therefore of critical importa...

For a long time, scientists thought that the differentiation of Mesenchymal Stem Cells (MSCs) into bone cells was dictated by growth factors. This manuscript shed light on other ligands that play a crucial role in regulating MSCs fate. In concrete terms, it was demonstrated that the osteoinductive effect of BMP-2 peptide is 2 folds improved in the presence of adhesive RGD peptide. Compared to previous works highlighting this synergistic cooperation between RGD and BMP-2 peptides, the main strength of this work lies to the use of primitive human cells (hMSCs) and well-defined biomimetic material surfaces (controlled surface roughness and peptide densities). This work provides valuable insights to develop custom-designed in vitro cell culture models, capable of targeting the desired cell response.