Establishment Of Vascular System Research Articles

Applications of nuclear reprogramming and directed differentiation in vascular regenerative medicine

As vertebrates proceed through embryonic development the growing organism cannot survive on diffusion of oxygen and nutrients alone and establishment of vascular system is fundamental for embryonic development to proceed. Dysfunction of the vascular system in adults is at the heart of many disease states such as hypertension and atherosclerosis. In this review we will focus on attempts to generate the key cells of the vascular system, the endothelial and smooth muscle cells, using human embryonic stem cells (hESCs) and human induced pluripotent stem cells (iPSCs). Regardless of their origin, be it embryonic or via somatic cell reprogramming, pluripotent stem cells provide limitlessly self-renewing populations of material suitable for the generation of multi-lineage isogenic vascular cells-types that can be used as tools to study normal cell and tissue biology, model disease states and also as tools for drug screening and future cell therapies.

Early embryonic vascular development

Establishment of a functional vascular system is imperative for normal embryonic growth and development. Building on the excellent descriptive studies of endothelial cell position and behavior, it is now possible to begin to define the mechanisms directing endothelial cell differentiation, commitment, migration and organization into a tube. What are the factors that control differentiation of mesoderm into angioblasts and what is needed for these angioblasts to organize into a vascular bed? These processes involve the careful orchestration of a diverse group of molecules including components of the extracellular matrix, cell adhesion receptors, growth factors and their receptors. This review has discussed just a few of the components that have been implicated as potentially important in the establishment of the vascular system. However, our understanding of how vessels form in the embryo is really quite rudimentary. We are just beginning to understand the delicate balance of both angiogenic and angiostatic processes that result in the intricate patterning and diverse function that is characteristic of developing endothelial cells. We have not even discussed important factors such as the role of blood flow and apoptosis in maintaining and remodeling vascular beds within the embryo nor have we addressed the development of endothelial heterogeneity in the mature animal [reviewed in Ref. 98]. There are certain to be new molecules identified as well as the delineation of new roles for known molecules. In addition, advances in genetic manipulation and improvements in both in vitro and in vivo model systems should provide important new insights into this critical process of vascular ontogeny.