Circulating Endothelial Progenitor and Mesenchymal Stromal Cells as Biomarkers for Monitoring Disease Status and Responses to Exercise.

Abstract

Noncommunicable chronic diseases, such as obesity, cardiovascular disease (CVD), and type 2 diabetes (T2D), pose significant health challenges globally. Important advances have been made in the understanding of the pathophysiologal mechanisms and treatment of noncommunicable diseases in recent years. Lack of physical activity is a primary contributor to many noncommunicable diseases including metabolic syndrome, T2D, CVD, and obesity. Certain diabetes medications and non-pharmaceutical interventions, such as physical activity and exercise, are shown to be effective in decreasing the CVD risks associated with heart disease, stroke, obesity, prediabetes, and T2D. The ability to measure and analyze circulating adult stem cells (ASCs) has gained particular interest due to their potential to identify at-risk individuals and implications in various therapeutics. Therefore, the purpose of this narrative review is to (1) provide an overview of ASCs; specifically endothelial progenitor cells (EPCs) and mesenchymal stromal cells (MSCs), (2) describe the responses of these cells to acute and chronic exercise, and (3) highlight the potential effect of exercise on EPCs and MSCs in aging and disease. EPCs are circulating cells, abundantly available in peripheral blood, bone marrow, and umbilical cord, and are defined by cell surface markers such as CD34+. EPCs are expected to play an important role in angiogenesis and neovascularization and have been implicated in the treatment of CVD. MSCs are essential for maintaining tissue and organ homeostasis. MSCs are defined as multipotent heterogeneous cells that can proliferate in vitro as plastic-adherent cells, have fibroblast-like morphology, form colonies in vitro, and can differentiate into ostyeoblasts, adipocytes, chondroblasts, and myoblasts. In the presence of aging and disease, EPCs and MSCs decrease in quantity and functional capacity. Importantly, exercise facilitates EPC differentiation and production from bone marrow and also helps to promote migration and homing to the hypoxic and damaged tissue which in turn improve angiogenesis and vasculogenesis. Similarly, exercise stimulates increases in proliferation and migratory activity of MSCs. Despite the reported benefits of exercise on EPC and MSC number and function, little is known regarding the optimal exercise prescription for aging and clinical populations. Moreover, the interactions between medications and exercise on EPCs and MSCs is currently unclear. Use of ASCs as a biomarker have the potential to revolutionize the management of patients with a variety of metabolic and obesity related disorders and also pro-inflammatory diseases. Further investigation of clinical entities are urgently needed to understand the implications of interventions such as exercise, diet, and various medications on EPC and MSC quantity and function in aging and clinical populations.