VE-cadherin-based matrix promoting the self-reconstruction of pro-vascularization microenvironments and endothelial differentiation of human mesenchymal stem cells

Regulating the secretion and endothelial differentiation of human mesenchymal stem cells (hMSCs) plays an important role in the vascularization in tissue engineering and regenerative medicine. In this study, a recombinant cadherin fusion protein consisting of a human vascular endothelial-cadherin extracellular domain and immunoglobulin IgG Fc region (hVE-cad-Fc) was developed as a bioartificial matrix for modulating hMSCs. The hVE-cad-Fc matrix significantly enhanced the secretion of angiogenic factors, activated the VE-cadherin-VEGFR2/FAK-AKT/PI3K signaling pathway in hMSCs, and promoted the endothelial differentiation of hMSCs even without extra VEGF. Furthermore, the hVE-cad-Fc matrix was applied for the surface modification of a poly (lactic-co-glycolic acid) (PLGA) porous scaffold, which significantly improved the hemocompatibility and vascularization of the PLGA scaffoldin vivo. These results revealed that the hVE-cad-Fc matrix should be a superior bioartificial ECM for remodeling the pro-vascularization extracellular microenvironment by regulating the secretion of hMSCs, and showed great potential for the vascularization in tissue engineering.