ABSTRACT

The vasculature is an essential component of every living tissue. Blood circulating through the vasculature delivers oxygen and nutrients while removing metabolic waste to sustain cell growth and function. The circulation additionally facilitates distal intercellular

CONTENTS

2.1 Introduction .......................................................................................................................... 17 2.1.1 Overview of the Human Vasculature ................................................................... 17 2.1.2 PCs: Origin, Characterization, and Location ....................................................... 19

2.2 Functional Roles of PC ........................................................................................................ 20 2.2.1 PC in Angiogenesis ................................................................................................. 20

2.2.1.1 PC-Recruitment to Sprouting Vessels .................................................... 20 2.2.1.2 PC Roles in Vessel Stabilization and Maturation ................................. 21 2.2.1.3 Functional Blocking of PCs Results in Abnormal Vessel Formation... 22

2.2.2 EC/PC Interactions in Mature Vessels .................................................................22 2.2.2.1 Physical Interactions between EC and PC .............................................22 2.2.2.2 Paracrine Signaling within the Vascular Wall ......................................23 2.2.2.3 Vascular Regulation of Inammation .................................................... 24

2.2.3 Tissue-Specic Roles of PCs ................................................................................... 26 2.2.3.1 PCs in Skin ................................................................................................. 26 2.2.3.2 PCs in Skin Pathologies ............................................................................ 27 2.2.3.3 PCs in the Lung .........................................................................................28 2.2.3.4 PCs in Pulmonary Pathologies................................................................28 2.2.3.5 PCs in the Eye and the Brain ...................................................................28 2.2.3.6 PCs in Pathologies of the Eye .................................................................. 29 2.2.3.7 PCs in Cerebral Pathologies..................................................................... 29 2.2.3.8 Overview .................................................................................................... 29

2.3 PC in Tissue Engineering ...................................................................................................30 2.3.1 Current Limitations in Tissue Engineering .........................................................30 2.3.2 Previous Methodologies for Vascular Engineering ............................................30 2.3.3 PC: A New Direction for Vascularizing Tissue-Engineered Constructs ......... 31

2.4 Conclusion ............................................................................................................................ 32 References ....................................................................................................................................... 32

communication; soluble factors and proteins released from cells are delivered beyond the diffusion barrier to enable endocrine communication. Pumping blood from the heart and the lungs to peripheral tissue for exchange requires vascular structures to vary spatially. The high-pressure large arteries proximal to the heart (aorta, carotid, etc.) are tasked with transporting oxygenated blood to distal regions of the body, and therefore require a thick, mechanically stable structure. These vessels are comprised of three distinct layers: the tunica intima, the luminal layer, the tunica media, the middle region, and the tunica adventitia, the outermost layer (Figure 2.1). An endothelial cell (EC) monolayer covers the luminal surface of the tunica intima, which is critical to prevent the formation of aberrant thrombi. The underlying layers, the tunica media and the tunica adventitia, are composed of extracellular matrix proteins including collagen and elastin, proteoglycans (PGs) and glycosaminoglycans (GAGs), with vascular smooth muscle cells (in the media) and broblasts (in the adventitia). Although there are differences in the organization and size of each of these layers when comparing the various classes of large vessels (elastic arteries, muscular arteries, veins, etc.), all large vessels maintain this characteristic three-layer structure (Humphrey 2002).