Endothelial Progenitor Cells A New Real Hope?

Chronic inflammatory diseases, such as cardiovascular diseases (CVDs), diabetes,Alzheimer’s disease (AD) and cancer, have a disproportionate prevalence withadvancing age owing to the continuous growth in the aging population. Thiscondition determines several medical, economic and social problems due to thedramatic increase in the number of affected individuals, who are not autonomous.Thus, research efforts are centred around reducing and/or delaying the onset andprogression of these diseases by researching new strategies for early prevention anddiagnosis. In this context, understanding the mechanisms involved in the tissue,organ protection and repair are imperative for the development of new preventivetreatments. Accordingly, medical research is pursuing new ways of trying to facethis imposing challenge, i.e. regenerative medicine with stem cells and progenitors,such as endothelial progenitor cells (EPCs). Since their discovery, EPCs haverapidly caught the attention of researchers for their ability to facilitate vascularrepair in different ischemic tissues, by contributing to neovascularization in severaltissue injury models. Interest has also heightened dramatically after evidence abouttheir capacity to counteract related CVD endothelium dysfunction. In addition,recent studies, using different animal models of cancer, suggested the importance ofbone marrow-derived EPCs (i.e. postnatal vasculogenesis) in tumor vascularizationand growth. EPCs are present in the peripheral blood; their levels are increased inresponse to certain signals/cytokines; and they home into the neovascular bed ofmalignant tissues. Furthermore, at the clinical level, evidence is emerging thatchanges in EPC levels might predict the efficacy of anticancer drug combinations,such as anti-angiogenic agents. On the basis of these observations, EPCs haveattractive potential diagnostic and therapeutic applications for malignant diseases.Additional recent evidence also suggests the possibility to adopt EPCs as prognosticbiomarkers for AD. It has been observed that patients with AD have reducedcirculating EPCs, suggesting that an anomalous capacity to regenerate endotheliumis associated with AD. In the case of diabetes, numerous groups have detecteddecreased EPC numbers and functionality in affected patients, confirmed bydecreased numbers of colony-forming units, decreased adhesion and migration anddecreased tubule formation. In addition, it has been found that strategies based onixthe administration of statins, angiotensin converting enzyme inhibitors, angiotensinreceptor blockers and peroxisome-proliferator-activating-receptor-c agonists,up-regulate and enhance both the EPC number and functionality.Emerging evidence also indicates that transplantation of EPCs is beneficial forthe recovery of ischemic cerebral injury. EPC-based therapy could open a newavenue for ischemic diseases. Currently, clinical trials for evaluating EPC transfusionin treating ischemic stroke are underway.However, much of the increasing evidence implicating progenitors in thesediseases is contrasting. Thus, their real role remains uncertain. This is compoundedby the necessity for a standardization of the different methodologies and protocolsfor characterizing, identifying and defining these cells, or their subsets. Thisproblem represents one of the major consequences of the large heterogeneity thatexists in data from the literature. In this monograph, some of these aspects arediscussed using research to give clear indications regarding EPC functions anddefinitions, as well as evidence to support the