Endothelial Progenitor Cells

Since endothelial progenitor cells (EPCs) were first described in 1997, there has been significant debate surrounding their definition and roles; but also agreement in their potential to develop as biomarkers and cytotherapies. EPCs participate in vascular repair and postnatal angiogenesis by differentiating into endothelial cells or by producing pro–angiogenic growth factors. Various subtypes of EPCs have been studied, such as CD34+VEGFR2+ blood circulating cells, cultured endothelial colony forming cells (ECFCs), and myeloid angiogenic cells (MACs). EPCs have therapeutic potential for revascularisation and vascular repair in ischemic diseases such as myocardial infarction and diabetic vascular complications. In this eBook, we compile evidence to enable their translation including strategies to enhance the number, homing ability to the injury site and function of EPCs.

This book explores the role of endothelial progenitor cells (EPCs) in the context of regenerative medicine (RegMed). In particular, it reveals the value of RegMed as a new TM branch intended to improve the health and quality of life, by restoring, maintaining or enhancing tissue and functions of organs. The book is divided into three chapters, the first of which describes the relevance of translational medicine (TM) as a new research approach to counteract the imposing challengeof age-related diseases. Of the diverse RegMed approaches, particular attention is paid to stem/progenitor cell-based therapies, their benefits and shortcomings, as well as to the description of types of stem and progenitor cells considered for regenerative cell therapies, such as EPCs as emerging candidates for RegMed applications. In turn, the second chapter outlines the clinical relevance of EPCs as both potential predictors, diagnostic and prognostic biomarkers of age-related diseases and therapeutic agents,discussing their advantages, disadvantages, and conflicting data. Chapter three proposes a potential roadmap for revising the findings and creating a clearer picture of valid data, which can provide support for various important aspects, i.e.isolating and characterizing EPCs by establishing standardized criteria for EPC research, identifying appropriate sub-populations for cell therapy, timing, dosing, priming of cells,and defining delivery modes for different applications. The book concludes with an overview of innovative strategies that could improve the efficacy of cell therapy at all levels, including cell priming, bio-nanotechnology, and tissue engineering.

The endothelium, a monolayer of endothelial cells, constitutes the inner cellular lining of the blood vessels (arteries, veins and capillaries) and the lymphatic system, and therefore is in direct contact with the blood/lymph and the circulating cells. The endothelium is a major player in the control of blood fluidity, platelet aggregation and vascular tone, a major actor in the regulation of immunology, inflammation and angiogenesis, and an important metabolizing and an endocrine organ. Endothelial cells controls vascular tone, and thereby blood flow, by synthesizing and releasing relaxing and contracting factors such as nitric oxide, metabolites of arachidonic acid via the cyclooxygenases, lipoxygenases and cytochrome P450 pathways, various peptides (endothelin, urotensin, CNP, adrenomedullin, etc.), adenosine, purines, reactive oxygen species and so on. Additionally, endothelial ectoenzymes are required steps in the generation of vasoactive hormones such as angiotensin II. An endothelial dysfunction linked to an imbalance in the synthesis and/or the release of these various endothelial factors may explain the initiation of cardiovascular pathologies (from hypertension to atherosclerosis) or their development and perpetuation. Table of Contents: Introduction / Multiple Functions of the Endothelial Cells / Calcium Signaling in Vascular Cells and Cell-to-Cell Communications / Endothelium-Dependent Regulation of Vascular Tone / Conclusion / References

This reference serves as the first source to gather current data from endothelial cell biologists in various disciplines to summarize recent progress in the field-providing a complete understanding of the endothelium in health and disease and demonstrating its potential as a therapeutic target.

We are delighted to offer this textbook to the scientific community, entitled Endothelial Progenitor Cells in Health and Diseases, which covers a timely topic in the rapidly evolving discipline of vascular biology. Written primarily for a life science audience and clinicians, the fundamentals of EPCs biology and the latest characterization and definition in health and diseases are introduced, followed by explanations of the most cutting-edge cell therapy methods to cure ischemic diseases. In Section One, endothelial cell progenitor isolation methods and biological characterization were reported. The discovery of this novel endothelial progenitor cells (EPC) concept has overturned the previous dogma which suggested that vasculogenesis could only occur during embryogenesis. In fact, both vasculogenesis and angiogenesis may potentially have a synergistic role in postnatal revascularization. Also, this chapter summarized recent advances in EPC biology such as biological function, origin, definition, and classification. Each EPC culture and isolation method is clearly defined to prevent confusion in EPC biology. Section Two focuses on EPC biological function alteration in cardiovascular diseases (CVD). Several large clinical trials have reported that the number and biological function are strongly associated with major adverse cardiovascular events. The diagnostic and prognostic potential of EPC is crucial in terms of CVD. In Section Three, biological dysfunction mechanisms of EPC and their scarcity in diabetic patients' peripheral blood were clearly described. Preclinical studies have shown that EPC-based therapy is feasible, safe, and efficacious in multiple disease states. Subsequently, this has led to several clinical trials demonstrating the feasibility and safety profile of EPC therapy against cardiovascular ischemic diseases. In Section Four, regenerative medicine pioneers discussed EPCs translation to the clinic and cell transplantation challenges along with their solutions. Personalized stem cell-based therapy approaches employing several clinical biomarkers, disease-related genetic-trait evaluation methods, and advanced analyses with state-of-the-art computational methods such as machine learning-based prediction can increase cell therapies' efficacy and decrease treatment costs. The last chapter in the book describes a therapeutic application of EPC-derived extracellular vesicles to cure CVD.

New experimental observations often require fresh concepts for their interpretation, and at times even changes of paradigms. This is the situation with the recent realization that circulating endothelial progenitor cells may have an important contribution to the maintenance and formation of new endothelium in adult organisms, in a surprisingly wide variety of situations. The classical paradigm of angiogenesis, centered on the notion of "sprouting" can hardly accommodate them. It was previously realized that it needs to be "stretched out" to include alternative mechanisms of microvascular development, such as intussusception and capillary fusion. However, a major debate where to reconsider the sprouting mechanism, and to promote alternative views, did not take place yet. The number of publications in this field increased exponentially in the last years. Nevertheless, the concepts and notions so much needed to describe and to explain the new observations are still scarce, and heterogeneous. Within the larger community dedicated to the study of angiogenesis, the researchers involved in investigation of circulating precursor endothelial cells biology represent a subgroup with specific preoccupations and opinions. Many of them did not meet each other so far, and no major scientific events have been dedicated before exclusively to their interests. For the above reasons, the idea to organize a symposium addressing the new developments in angiogenesis research was received with enthusiasm by all those involved in its preparation.

The book provides a comprehensive overview of selected topics in microcirculation, from physiology to pathophysiology including molecular mechanisms and clinical aspects. It contains 10 chapters written by reputed authors, which comprehensively sum up the current knowledge and some interesting new insights in the field of microcirculation. It will be useful to a broad range of audience, from students to highly profiled experts, helping them to expand their knowledge on microcirculation and opening up additional questions for further investigation.