L20	Endothelial tissue engineering.
S.Levenberg
Technion, Haifa, IL.

Vascularization of engineered tissue constructs, using endothelial cells or progenitors seeded on biodegradable polymer scaffolds, can provide new approach for inducing vessel network formation in vitro and in vivo. Embryonic stem cells have the capability to differentiate and form blood vessels de novo in a process called vasculogenesis. We have shown that human embryonic stem cells (hESC) can differentiate into endothelial cells forming vascular-like structures when formation of embryoid bodies is induced and that these cells can be isolated and grown in culture. The embryonic endothelial cells can differentiate into vessel-like structures in vitro, and in vivo, when seeded on polymer scaffolds and implanted subcutaneously into immuno-deficient mice. We have also developed an approach to engineer three-dimensional human tissue structures using early differentiating hESC and further inducing their differentiation in a supportive three-dimensional environment such as PLLA/PLGA polymer scaffolds. We have shown that variation of growth factor conditions induced formation of complex tissue structures with features of various committed embryonic tissues and demonstrated the presence of three-dimensional capillary-like networks displaying endothelial cell-associated surface molecules throughout the tissue construct. In vivo, the hESC constructs recruited and anastamosed with the host vascular system. To improve vascularization of engineered skeletal muscle tissue we induced endothelial vessel networks in engineered skeletal muscle tissue constructs using a three-dimensional multi-culture system consisting of myoblasts, embryonic fibroblasts and endothelial cells, co seeded on highly porous, biodegradable polymer scaffolds. Analysis of the conditions for induction and stabilization of the vessels in vitro, showed that addition of embryonic fibroblasts promoted formation and stabilization of the endothelial vessels. In vivo results show that pre-vascularization improved vascularization, blood perfusion and survival of the muscle tissue construct after transplantation.

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