INDUCTION OF EMBRYONIC VASCULOGENESIS BY BFGF AND LIF IN-VITRO AND IN-VIVO

The de novo formation of blood vessels (vasculogenesis) is an integral part of embryogenesis. Elucidation of the role of cytokine cooperatio n in vasculogenesis may lead to a better understanding of organogenesi s, blood vessel regulation during tumorigenesis, and tissue injury. We have used embryonic stem cells to derive an endothelial cell line, de signated IEM, which expresses a range of endothelial markers, includin g Von Willibrand Factor VIII related antigen, vascular cell adhesion m olecule, platelet-endothelial cell adhesion molecule (CD31), and recep tors for acetylated low-density lipoprotein. More importantly, IEM cel ls can be induced upon exposure to combinations of basic fibroblast gr owth factor and leukemia inhibitory factor (LIF) to proliferate and un dergo vasculogenesis in vitro, resulting in the formation of vascular tubes and microcapillary anastomoses. Moreover, exposure to both cytok ines conditionally permits IEM cells to specifically chimerize microva scular endothelium in vivo following blastocyst injection. These resul ts indicate that bFGF and LIF together contribute to the induction and support of embryonic vasculogenesis in an isolated endothelial cell l ine. Our results provide evidence that combined actions of bFGF/LIF ma y play a role in mechanisms controlling blood vessel development. (C) 1996 Academic Press, Inc.