Vascularization and Improved In Vivo Survival of VEGF-Secreting Cells Microencapsulated in HEMA-MMA

Abstract

Vascularization caused by encapsulated cells engineered to secrete vascular endothelial growth factor (VEGF) improved the in vivo survival of the encapsulated cells in a syngeneic mouse Matrigel plug model. Murine fibroblast cells (L929) were engineered to secrete recombinant human vascular endothelial growth factor (rhVEGF(165)). Transfected and nontransfected L929 cells were microencapsulated in a 75:25 hydroxyethyl methacrylate-methyl methacrylate (HEMA-MMA) copolymer. Capsules containing transfected cells induced vascularization in vivo at 1 and 3 weeks postimplantation. In histological sections, a significant positive correlation was seen between the number of capsules and blood vessel density for VEGF-secreting cell capsule implants. New vessels, many positively stained for smooth muscle cells and pericytes, were seen surrounding these VEGF-secreting cell capsule explants. Few vessels were seen in nontransfected L929 capsule implants. The viability of transfected and nontransfected encapsulated cells was assessed on explantation. Although the viability of all encapsulated cells decreased at both 1 and 3 weeks, encapsulated VEGF-secreting cells retained more of the viability than did encapsulated nontransfected control cells. Genetically modified cells promoted vascularization in this context and appeared to enhance the viability of the encapsulated cells, although the extent of the functional benefit was less than expected. Additional effort is required to enhance the benefit, to quantify it, and to understand further the host response to HEMA-MMA microencapsulated cells and tissue constructs, more generally.