Frontiers in Stem Cell and Regenerative Medicine Research: Volume 5

Atta-ur-Rahman, Shazia Anjum, Atta-ur-Rahman, Shazia Anjum

• Publisher: Bentham Science Publishers
• Year: 2017
• Print ISBN:
  9781681084763
• eBook ISBN:
  9781681084756
• Topic: Ciencias biológicas
• Subtopic: Biología celular

Stem cell and regenerative medicine research is a hot area of research which promises to change the face of medicine as it will be practiced in the years to come. Challenges in the 21st century to combat diseases such as cancer, Alzheimer and related diseases may well be addressed employing stem cell therapies and tissue regeneration. Frontiers in Stem Cell and Regenerative Medicine Research is essential reading for researchers seeking updates in stem cell therapeutics and regenerative medicine.
The fifth volume of this series features reviews on vascular regeneration, neuronal tissue grafting in animal CNS disease models, template mediated biomineralization in bones, corneal endothelium differentiation and stem cell uses for managing hepatocellular carcinoma.

Stem/Progenitor Cells in Vascular Regenerative Medicine: Mechanisms, Signalling and Translation

INTRODUCTION

Human blood vessels consist of a monolayer of endothelial cells (ECs) that is often associated with mural cells including smooth muscle cells (SMCs) and pericytes, which together compose the indispensable part of the vascular system. The vascular system acts as the conduit transporting oxygen, nutrients, hormones and growth factors while removing metabolic waste products throughout the whole body. Vascular integrity hence plays an essential role in organ development as well as in the maintenance of tissue homeostasis. Vasculature has high plasticity, most notably in its ability in de novo vessel formation (vasculogenesis) and sprouting (angiogenesis), which are both important in healthy tissue repair. Disruption in vascular homeostasis can lead to numerous cardiovascular pathologies [1].

Cardiovascular disease is the leading cause of death in the world. Endothelial dysfunction and vascular remodelling are critical in the development of atherosclerosis, which can proceed to a whole range of associated cardiovascular diseases including coronary heart disease, stroke, peripheral vascular diseases (PVDs), unstable angina and sudden cardiac death [2, 3]. Many of these conditions are the results of disrupted vascular supply caused by vascular remodelling associated with atherosclerosis, leading to irreversible cell losses and organ failure. Vascular regeneration, which includes the restoration of normal vascular function and structure, the rejuvenation of vascular senescence and the growth of de novo blood vessels, represents an effective therapeutic strategy in relieving symptoms of tissue ischemia and preventing the eventual target-organ damages. However, difficult challenges confer upon vascular regeneration, mainly due to inadequate means to efficiently and rapidly regenerate ECs for replacement therapy.

Traditionally, cells within the adult vasculature were considered to be terminally differentiated. The principal sources of vascular regeneration were considered to be the recruitment of bone marrow-derived circulating progenitors and the re-entry of mature cells on the vascular wall back into the cell cycle. Recent efforts in investigating the dynamic nature of blood vessels have also established vessel wall as a reservoir of multipotent resident stem/progenitor cells that can be differentiated towards ECs and SMCs. Their endogenous activities could be important in repairing injured endothelium, thereby restoring the integrity of the vessel and its function. Moreover, enormous interests are also bestowed upon activating vascular lineage differentiation of pluripotent embryonic stem cells (ESCs) and the more lineage-committed “adult” stem/progenitor cells (e.g. circulating and vascular wall resident stem/progenitor cells, mesenchymal stem cells (MSCs) and endothelial progenitor cells (EPCs)) for vascular repairs and for generation of tissue-engineered blood vessels (TEBVs) [4, 5]. Recent advances in somatic cell reprogramming into functional vascular cells, either through the intermediate pluripotent state (induced pluripotent stem cell (iPSCs)) or by direct lineage conversion, offer additional strategies for vascular regeneration [6, 7]. Therefore a lot of efforts have also been placed on designing the most robust and efficient strategies in generating key vascular cells from these various potential cell sources. Major strides in the development of advanced vessel scaffolds made from biodegradable polymers, native matrices or other biological materials have further broadened the toolkits for vascular regenerative cell therapy. Finally, researchers continue to uncover novel insights in the molecular mechanisms underlying many vascular pathogenesis through employing patient-specific iPSC-derived vascular cells as in vitro disease models. This approach is remarkably useful in identifying new drug targets and enabling the delivery of ‘personalised medicine’ by offering new patient-specific pharmacological, genetic and cellular therapies. This chapter will discuss the recent advances in vascular differentiation of adult stem/progenitor cells and pluripotent stem cells (PSCs), direct lineage conversion of somatic cells, vascular tissue engineering and the uses of iPSC-based vascular disease modelling to uncover novel therapeutic strategies.

VASCULAR SYSTEM

Blood Vessels and Vascular Cells

The vascular system comprises three anatomically and functionally distinct components: arteries, veins and capillaries. The arterial system is primarily involved in the delivery of oxygenated blood and nutrients from the heart to target tissues and organs. It has higher blood pressure and has a higher composition of SMCs underlying the endothelium. The capillaries allow the exchange of oxygen and nutrients with metabolic wastes between the blood and the tissues. The venous system functions by carrying deoxygenated blood, waste products, and other factors released by the tissues back to the heart. Veins tend to have larger luminal areas and thinner vessel walls compared to arteries and have valves to complement the pressure changes.

The walls of the vessels are generally composed of three layers- tunica intima, tunica media and tunica adventitia. In elastic and muscular arteries the tunica intima forms the innermost layer that comprises a single layer of ECs with associated connective tissues (sub-endothelial layer) lying on an internal elastic lamina, and acts as a selective permeable barrier between the blood and the vessel wall. The tunica media forms the middle layer of the vessel wall and comprises circumferentially-arranged SMCs enclosed by a layer of external elastic lamina, providing supports to the vessels and regulating blood flow and pressure via controlling the vessel diameter. The tunica adventitia is the outermost layer that is primarily composed of connective tissues and matrix-secreting fibroblasts, which serves to provide structural support to the vessels and helps to anchor them in place to fit into the surrounding structure. On the contrary, non-muscular vessels such as capillaries are only made up of a single layer of ECs on an internal elastic lamina.

The vascular system is developed embryonically through three major processes: vasculogenesis, angiogenesis and arteriogenesis [8 - 10]. Vasculogenesis is the de novo formation of vascular structures by the migration and differentiation of mesoderm-derived endothelial precursors (angioblasts) to the sites of vascularisation where they coa...

Table of contents

• Welcome
• Table of Contents
• Title Page
• BENTHAM SCIENCE PUBLISHERS LTD.
• PREFACE
• List of Contributors
• Tissue Engineering in Vascular Medicine
• Stem/Progenitor Cells in Vascular Regenerative Medicine: Mechanisms, Signalling and Translation
• Functional Integration of Neural Tissue Grafted in Animal Models of CNS Disease
• Functionalized 3D Scaffolds for Template-mediated Biomineralization in Bone Regeneration
• Current State and Future Perspectives in Corneal Endothelium Differentiation
• The Role of Stem Cells in the Management of Hepatocellular Carcinoma