Study of endothelial progenitor cells as a non-invasive strategy o detect endothelial alterations in patients with idiopathic thromboembolism

BACKGROUND Thromboembolism is defined idiopathic (ITE) when occurring without triggering circumstances. Inflamed and dysfunctional endothelium may play a pathogenic role in the disease. Endothelial progenitor cells (EPCs) are newly identified bone-marrow-derived cells crucial to endothelial homeostasis. Yet, their analysis in the blood may represent a novel, non-invasive strategy to study the endothelial compartment. In this study, we investigated possible alterations of circulating EPCs that may reflect endothelial perturbation, in ITE patients. METHODS EPCs were isolated and expanded ex-vivo as endothelial colony-forming cells (ECFCs), using a method recently optimized in our lab. ECFCs were cultured from peripheral blood mononuclear cells (PBMCs) obtained from 13 ITE patients and 20 matched controls. Cultures were analyzed for efficiency of ECFC colony isolation, cell viability, morphology, immunophenotype, cytokine production, migration, in-vitro vasculogenesis. RESULTS ECFC colonies were isolated from ITE patients with the same efficiency as controls, as assessed as number of colonies and time of colony appearance starting from PBMC seeding. ECFC colonies from ITE patients were smaller and characterized by a high rate of early mortality, with cultures undergoing cell senescence within the first passage in a higher proportion of cases in ITE than controls (p< 0.05). CONCLUSIONS The preliminary results of this study indicate alterations in the growth of EPCs isolated from ITE patients that may indeed contribute to impairment of endothelial integrity in these patients. A full characterization of expanded ECFCs, still in progress, may further reveal functional defects of these cells that may possibly hinder the physiologic antithrombotic function of endothelium.