The Effect of Soluble Recombinant Protein Dll4-Fc on the Functional Activity of Endothelial Cells In Vitro and Vascularization In Vivo

Abstract

Restoration of the microvasculature system is necessary for wound healing. Increased angiogenesis in damaged tissue can positively affect the speed and quality of its recovery. The paper analyzes the effect of the soluble recombinant protein Dll4-Fc on the functional activity of human endothelial cells HUVEC, HUVEC-56, and ECV-304 cultivated under two-dimensional (2D) and three-dimensional (3D) conditions in vitro and the formation of the capillary network during wound healing in rats in vivo. The goal was possible use of Dll4-Fc protein in biomedical cell products aimed at stimulating the growth of blood vessels in the process of damaged-organ and -tissue repair. The results showed that Dll4-Fc did not affect the proliferative and migratory activity of endotheliocytes cultivated under 2D conditions. However, a positive effect of Dll4-Fc on the morphology of the endotheliocyte layer and formation of capillary-like structures was revealed in 3D ECV-304 cells cultivated on the surface of collagen gel. For the first time, the positive effect of the “dermal equivalent” in a composition with endothelial cells of the human umbilical HUVEC and Dll4-Fc on the formation of blood vessels in the area of healing was shown.