Presentation 8
Vascular Tissue Engineering Using Human Embryonic Stem Cells
Dr. Shulamit Levenberg
Biomedical Engineering Department, Technion.
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Vascularization of engineered tissue constructs, using endothelial cells seeded on biodegradable polymer scaffolds, can provide new approach for including vessel network formation in-vitro and in-vivo. We have shown that human embryonic stem cells (hESC) can differentiate into endothelial cells forming vascular-like structures 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 vivio.We have also developed an approach to engineer three-dimensional (3D) human tissue structures using early differentiating hESC and further inducing their differentiation in a supportive 3D 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 3D 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 3D multi-culture system consisting of myoblasts, embryonic fibroblasts and endothelial cells, co seeded on 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 improves vascularization, blood perfusion and survival of the muscle construct after transplantation.
