Open Access Medical Books



Edited by Dan T. Simionescu and Agneta Simionescu .

238  pages . 
Open Access .

The formation, development and persistence of most major organs and tissues depend on adequate vascularization. Blood vessels are among the first functional structures that form during embryonic development. Defects in blood vessel formation frequently lead to congenital malformations which need to be corrected by surgery or by using regenerative medicine approaches. After birth, existing blood vessels grow in size but new blood vessel formation is poorly represented in healthy individuals. This status quo is disturbed in numerous pathological conditions such as wound healing, rheumatoid arthritis, retinopathy, ischemia, and tumor and metastasis. Tumor growth depends greatly on extensive vascularization, and thus cancer research has focused tremendously on agents capable of blocking blood vessel formation.
During aging, blood vessels deteriorate slowly due to lipid and calcium deposition, inflammation, auto-immune reactions, and infections, potentially affecting all major organs and systems. Vascular diseases are a leading cause of morbidity and mortality worldwide and diseased blood vessels require surgical replacement with engineered devices. Tissue engineering and regenerative medicine approaches are diligently working on two main avenues: first, generation of living blood vessels of various calibers to serve as surgical replacements and second, development of vascularized living tissue substitutes with intrinsic 3D blood vessel networks to sustain effective organ perfusion.
New blood vessels may arise by two processes, vasculogenesis and angiogenesis. Endothelial cells are fundamental and common to both processes: however they differ in location, mechanisms of initiation and source of precursor cells. Vasculogenesis is a term describing the general process of de novo blood vessel formation during embryologic development of the cardiovascular system. This refers to two distinct inception scenarios: first, production of new endothelial cells in a developing embryo followed by development of a primordial vascular tree and second, generation of blood vessels in an adult avascular tissue area from precursor cells that migrate and differentiate to endothelial cells as a response to local signals.
Angiogenesis is the process by which new blood vessels form by “sprouting” of endothelial cells from pre-existing blood vessels; after “branching”, these new “trees” are then reorganized, “pruned” and remodeled to eventually become 3D networks and also larger diameter vessels. Since this process is graphically similar to the growth and development of trees, there is no wonder that most terms used in angiogenesis are derived from the science of forestry.
Before the discovery of endothelial progenitor cells (EPCs) in the late 90’s, the general consensus was that de novo vasculogenesis was restricted to the embryonic development arena and angiogenesis was only limited to growth and remodeling of adult vascular tissue. It is now known that as a response to injury, EPCs that normally reside in the bone marrow are mobilized into the circulation, migrate to avascular areas, differentiate into mature endothelial cells and develop vascular networks. In addition, bone marrow derived stem cells can act as “cytokine factories” and boost remodeling by secreting growth factors that help mature the developing “vascular tree”. These cells have now become a central theme around which tissue engineering and regenerative medicine revolves. Vascular tissue engineering using scaffolds and stem cells has made great progress in recent years, highlighted by numerous successful animal experiments and recent clinical trials.
As shown above, basic and applied research in vasculogenesis and angiogenesis has come a long way and has elicited tremendous interest. The study of blood vessel formation is an essential component of embryonic development, congenital malformations, degenerative diseases, and cancer. It is probably almost impossible to contain and review all the research performed in this field in one single book.
The purpose of this book is to highlight novel advances in the field, focusing on four aspects of relevance. Esteemed authors from the USA, Europe and Asia, selected from a variety of fields summarize knowledge in their area of expertise and also contribute with authentic original experimental data to each chapter. The first section focuses on the early stages of human embryogenesis, development of the cardiac vasculature, the fetal lung and a novel signaling marker for vessel formation. This is followed by a section that focuses on regulation of EPCs and their role in diabetic vascular diseases.
The role of vasculogenesis and angiogenesis in cancer is highlighted by two chapters that reveal the power of animal models and inhibitors of vasculogenesis and angiogenesis. Finally, looking towards the future, the last chapter highlights use of current knowledge towards regeneration of blood vessels using precursor cells, scaffolds and the proper mechanical cues.
This book is a good source of information for scientists interested in the intricacies of blood vessel formation, maturation, disease and replacement. It is also adequate for graduate students and medical students who wish to acquire basic updated information in the field.
Strolling through it, the reader will appreciate the crucial involvement of various precursor cells, starting with the primordial vascular cells in the embryo, the mesenchymal progenitor cells in healing and pathology and the lessons one can learn from the extraordinary ability of the cancer cells to manipulate blood vessel formation.

We are hoping that this book will help raise interest in the field and will entice new investigators to dwell into the complex and fascinating world of blood vessel formation, from the early days of embryonic development to the prospects of creating blood vessels in vitro for use as surgical replacements.

Dan T. Simionescu
Agneta Simionescu
Clemson University, Clemson, SC,



Part 1 Developmental Biology .

 1 Human Embryonic Blood Vessels: What Do They Tell Us About Vasculogenesis and Angiogenesis? 3 Simona Sârb, Marius Raica and Anca Maria Cîmpean

 2 Cardiac Vasculature: Development and Pathology 15 Michiko Watanabe, Jamie Wikenheiser, Diana Ramirez-Bergeron, Saul Flores, Amir Dangol, Ganga Karunamuni, Akshay Thomas, Monica Montano and Ravi Ashwath

 3 Vascular Growth in the Fetal Lung 49 Stephen C. Land

 4 Apelin Signalling: Lineage Marker and Functional Actor of Blood Vessel Formation 73 Yves Audigier

Part 2 Endothelial Progenitor Cells .

 5 Regulation of Endothelial Progenitor Cell Function by Plasma Kallikrein-Kinin System 99 Yi Wu and Jihong Dai

 6 Vasculogenesis in Diabetes-Associated Diseases: Unraveling the Diabetic Paradox 107 Carla Costa

Part 3 Cancer Research .

 7 Modeling Tumor Angiogenesis with Zebrafish 133 Alvin C.H. Ma, Yuhan Guo, Alex B.L. He and Anskar Y.H. Leung

 8 Therapeutic and Toxicological Inhibition of Vasculogenesis and Angiogenesis Mediated by Artesunate, a Compound with Both Antimalarial and Anticancer Efficacy 145 Qigui Li, Mark Hickman and Peter Weina

Part 4 Regenerative Medicine .

 9 The Mechanics of Blood Vessel Growth 187 Rui D. M. Travasso

 10 A Novel Adult Marrow Stromal Stem Cell Based 3-D Postnatal De Novo Vasculogenesis for Vascular Tissue Engineering 205 Mani T. Valarmathi and John W. Fuseler

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Published by: younes younes - Saturday, May 18, 2013


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