Role of the microenvironment in the specification of endothelial progenitors derived from embryonic stem cells

Embryonic stem (ES) cells are pluripotent cells capable of differentiating in all the cell types present in a living organism. They derive from the inner cell mass of blastocysts of different species including humans. Given their unlimited potential, ES cells represent an invaluable resource of different cell types for transplantation and tissue engineering applications. However, in order to accomplish these therapeutic purposes, efficient and controlled in vitro systems of directing ES cell differentiation are mandatory. ES cell differentiation is strongly influenced by physical, chemical and cellular signals provided by the local microenvironment. Understanding the relationships occurring between differentiating cells and surrounding environment is pivotal for a successful ES cells-based therapy. This review describes three different methods of in vitro differentiation of ES cells by outlining the environmental elements required for endothelial fate specification. For each system, the efficiency of endothelial differentiation, the accessibility and the advantages are discussed. The main conclusion that arises from this analysis is that the knowledge of the role played by microenvironment in cell fate determination is essential to control and take advantage of ES cells potential.