Abstract

Prevascularized cell sheets are widely used in tissue engineering; however, enhancing their angiogenic potential within hypoxic microenvironments remains a significant challenge. In this study, we employed genetic manipulation to upregulate Sestrin2 (SESN2) expression in human umbilical vein endothelial cells (HUVECs) and investigated its effect on their angiogenic potential under hypoxic conditions. Transwell migration and Matrigel tube formation assays confirmed that SESN2 significantly promoted proliferation, migration, and tube formation of HUVECs under hypoxia, thereby enhancing angiogenesis. Furthermore, HUVECs overexpressing SESN2 were seeded onto cell sheets, and immunofluorescence staining for CD31 revealed increased lumen formation compared with the control group. SESN2 was also found to promote the secretion of vascular endothelial growth factor A and platelet-derived growth factor BB in vitro. Subsequent subcutaneous implantation studies demonstrated that prevascularized cell sheets with SESN2 overexpression enhanced angiogenesis and promoted the formation of functional blood vessels. In conclusion, SESN2 improves the vascularization capacity of tissue-engineered grafts in hypoxic environments, thereby facilitating successful transplantation of engineered tissues.