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Christian van Dijk

Project description

All tissues in the human body need to be vascularized to provide oxygen and nutrients to the cells and remove waste metabolites. This is immediately the bottleneck of tissue engineering, larger constructs need to be vascularized. The current challenge is not only the co-culture of the vasculature and the tissue of interest, both blood vessels and tissue need to be functional. Blood vessels of different diameter are needed to get a functional vascular tree in the tissue and these vessels need to withstand hemodynamic forces like shear stress and wall stretch. Tissue engineered blood vessels could aid in establishing better vascular access to the circulatory system. Grafts and constructs from different materials, derived from different techniques could be used to aid in development and maturation of blood vessels. Our focus is the use of vascular organoids as primary source of endothelial cells and supporting mural cells. These 3D cultured spheroids are derived from human pluripotent stem cells and are able to recapitulate the different cells of blood vessels with patient specific characteristics. When seeded on a graft or scaffolds we aim to get an in vitro blood vessel which can be used either as autologous transplant or in vitro model. iPSC derived vascular organoids are more immature then in vivo adult cells and will therefore react differently in in situ tissue engineering. Pre-seeding of the grafts or scaffolds with vascular organoids followed by hemodynamic stimulation in vitro could help to mature the new blood vessel and help specialize its function towards an arterial or venous phenotype. Furthermore, combination of vascular organoids and renal organoids lead to a more complex 3D co-culture in which functional kidney cells and a functional circulatory system mimic the kidney function.

 

Techniques: 3D cell culture, Confocal imaging
Key words: Vascularization, Tissue engineering, Vascular organoids, 3D culture