Transplantation of microencapsulated cells expressing VEGF improves angiogenesis in implanted xenogeneic acellular dermis on wound.

ABSTRACT

BACKGROUND: Cell-based gene therapy using cells that express angiogenic factors is an alternative technique for therapeutic angiogenesis in transplantation of xenogeneic acellular dermis matrix (ADM). However, immune rejection is a substantial obstacle to implantation of genetically engineered allogeneic or xenogeneic cells. OBJECTIVE: To evaluate application of microencapsulated cells that express vascular endothelial growth factor (VEGF) in xenogeneic ADM transplants to improve wound angiogenesis and healing. MATERIALS AND METHODS: NIH3T3 cells were genetically modified to secrete VEGF and enveloped in semipermeable microcapsules. Microencapsulated VEGF-NIH3T3 cells were implanted in defects on the dorsa of guinea pigs with xenogeneic ADM and autologous split-thickness skin grafts. Cell structure and microencapsulation were observed at microscopy, and expression of VEGF was detected using an enzyme-linked immunosorbent assay (ELISA) and immunochemistry. Extent of angiogenesis in the ADM and the survival rate of the composite skin were evaluated after 2 weeks. In addition, expression of human VEGF and CD31 in the implanted acellular dermis was assessed, and microvessel density was calculated. RESULTS: Microencapsulated VEGF-expressing NIH3T3 cells were prepared successfully, and demonstrated proliferation and viability, and expressed VEGF both in vitro and in vivo. Extent of angiogenesis and survival rate of the composite skin containing the microencapsulated VEGF-expressing cells were significantly greater than in controls. Microencapsulated VEGF-expressing NIH3T3 cells augmented early angiogenesis in ADM implanted on wound and improved healing. CONCLUSION: Microencapsulated xenogeneic cell-based gene therapy may be a novel approach to therapeutic angiogenesis in transplantation of xenogeneic ADM skin.