The Effect of Soluble Recombinant Protein Dll4-Fc on the Functional Activity of Endothelial Cells In Vitro and Vascularization In Vivo
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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.
Keywords:Notch signaling Dll4-Fc protein angiogenesis endothelial cells dermal fibroblasts dermal equivalent biomedical cell product
This study was supported by the Russian Foundation for Basic Research, project no. 15-29-04852/15-ofi-m.
COMPLIANCE WITH ETHICAL STANDARDS
Conflict of interests. The authors declare that they have no conflict of interest.
Statement of compliance with standards of research involving humans as subjects. This article does not contain any studies involving human participants performed by any of the authors.
Statement on the welfare of animals. All procedures were carried out according to the rules for the treatment of laboratory animals set out by the OLAWNIH document (identification no. F18-00380, Institute of Cytology, Russian Academy of Sciences).
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