Mesenchymal stem cells support human vascular endothelial cells to form vascular sprouts in human platelet lysate-based matrices

Abstract

AbstractDuring tissue regeneration, mesenchymal stem cells can support endothelial cells in the process of new vessel formation. For a functional interaction of endothelial cells with mesenchymal stem cells a vascular inductive microenvironment is required. Using a cellular model for neo-vessel formation, we could show that newly formed vascular structures emanated from the embedded aggregates, consisting of mesenchymal stem cells co-cultured with human umbilical vein endothelial cells, into the avascular HPL-based matrices bridging distances up to 5 mm to join with adjacent aggregates with the same morphology forming an interconnected network. These newly formed vascular sprouts showed branch points and generated a lumen as sign of mature vascular development. Mesenchymal stem cells in fluid phase could bind to and interact with adherent human umbilical vein endothelial cells when a shear-force of 2 dyne/mm2 was applied in the flow chamber using a Bioflux®200 device. Under these conditions, mesenchymal stem cells bind to human umbilical vein endothelial cells previously damaged by laser beam irradiation to interact and shed particles.In conclusion, we observed that mesenchymal stem cells support human umbilical vein endothelial cells to form new vessels in HPL-based matrices when co-cultured in spherical aggregates to generate complex vascular networks in a primarily avascular scaffold and bind to the damaged cells under shear-force to eventually aid in their regeneration.