Local Release of VEGF Using Fiber Mats Enables Effective Transplantation of Layered Cardiomyocyte Sheets

Abstract

Cell sheet transplantation is a key tissue engineering technology. A vascular endothelial growth factor (VEGF)-releasing fiber mat is developed for the transplantation of multilayered cardiomyocyte sheets. Poly(vinyl alcohol) fiber mats bearing poly(lactic-co-glycolic acid) nanoparticles that incorporate VEGF are fabricated using electrospinning and electrospray methods. Six-layered cardiomyocyte sheets are transplanted with a VEGF-releasing mat into athymic rats. After two weeks, these sheets produce thicker cardiomyocyte layers compared with controls lacking a VEGF-releasing mat, and incorporate larger-diameter blood vessels containing erythrocytes. Thus, local VEGF release near the transplanted cardiomyocytes induces vascularization, which supplies sufficient oxygen and nutrients to prevent necrosis. In contrast, cardiomyocyte sheets without a VEGF-releasing mat do not survive in vivo, probably undergo necrosis, and are reduced in thickness. Hence, these VEGF-releasing mats enable the transplantation of multilayered cardiomyocyte sheets in a single procedure, and should expand the potential of cell sheet transplantation for therapeutic applications.

Keywords: VEGF; cell sheet; electrospun fiber; regenerative medicine; tissue engineering.