Endothelial Progenitor Cells A New Real Hope?

Abstract

Chronic inflammatory diseases, such as cardiovascular diseases (CVDs), diabetes, Alzheimer’s disease (AD) and cancer, have a disproportionate prevalence with advancing age owing to the continuous growth in the aging population. This condition determines several medical, economic and social problems due to the dramatic increase in the number of affected individuals, who are not autonomous. Thus, research efforts are centred around reducing and/or delaying the onset and progression of these diseases by researching new strategies for early prevention and diagnosis. In this context, understanding the mechanisms involved in the tissue, organ protection and repair are imperative for the development of new preventive treatments. Accordingly, medical research is pursuing new ways of trying to face this imposing challenge, i.e. regenerative medicine with stem cells and progenitors, such as endothelial progenitor cells (EPCs). Since their discovery, EPCs have rapidly caught the attention of researchers for their ability to facilitate vascular repair in different ischemic tissues, by contributing to neovascularization in several tissue injury models. Interest has also heightened dramatically after evidence about their capacity to counteract related CVD endothelium dysfunction. In addition, recent studies, using different animal models of cancer, suggested the importance of bone marrow-derived EPCs (i.e. postnatal vasculogenesis) in tumor vascularization and growth. EPCs are present in the peripheral blood; their levels are increased in response to certain signals/cytokines; and they home into the neovascular bed of malignant tissues. Furthermore, at the clinical level, evidence is emerging that changes in EPC levels might predict the efficacy of anticancer drug combinations, such as anti-angiogenic agents. On the basis of these observations, EPCs have attractive potential diagnostic and therapeutic applications for malignant diseases. Additional recent evidence also suggests the possibility to adopt EPCs as prognostic biomarkers for AD. It has been observed that patients with AD have reduced circulating EPCs, suggesting that an anomalous capacity to regenerate endothelium is associated with AD. In the case of diabetes, numerous groups have detected decreased EPC numbers and functionality in affected patients, confirmed by decreased numbers of colony-forming units, decreased adhesion and migration and decreased tubule formation. In addition, it has been found that strategies based on ix the administration of statins, angiotensin converting enzyme inhibitors, angiotensin receptor 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 for the recovery of ischemic cerebral injury. EPC-based therapy could open a new avenue for ischemic diseases. Currently, clinical trials for evaluating EPC transfusion in treating ischemic stroke are underway. However, much of the increasing evidence implicating progenitors in these diseases is contrasting. Thus, their real role remains uncertain. This is compounded by the necessity for a standardization of the different methodologies and protocols for characterizing, identifying and defining these cells, or their subsets. This problem represents one of the major consequences of the large heterogeneity that exists in data from the literature. In this monograph, some of these aspects are discussed using research to give clear indications regarding EPC functions and definitions, as well as evidence to support the problem of their characterization. In addition, recent findings on their role as disease biomarkers and exogenous or autologous cell therapy are provided. Certainly, limitations are also stressed. Based on these observations, this monograph, structured in