Formation of vascularized meniscal tissue by combining gene therapy with tissue engineering

Abstract

Ingrowth of host blood vessels into engineered tissues has potential benefits for successful transplantation of engineered tissues as well as healing of surrounding host tissues. In particular, the use of a vascularized bioengineered tissue could be beneficial for treating injuries to the meniscus, a structure in the knee where the lack of a vascular supply is associated with an inadequate healing response. In this study, gene transfer using an adenovirus vector encoding the hepatocyte growth factor gene (AdHGF) was used to induce blood vessel formation in tissue-engineered meniscus. Bovine meniscal cells were treated with AdHGF, a vector encoding a marker gene E. coli beta-galactosidase (Adbetagal), or no virus. Cells were seeded onto poly-glycolic acid felt scaffolds and then transplanted into the subcutaneous pouch of athymic nude mice for 8 weeks. Expression of the marker gene and HGF was detectable for several weeks after gene transfer. Ink injection studies showed that AdHGF-treated meniscal cells formed tissue which contained fourfold more blood vessels at 2 weeks (p < 0.02) and 2.5-fold more blood vessels at 8 weeks (p < 0.001) posttransplantation than controls. This study demonstrates the feasibility of using adenovirus-mediated gene transfer to engineer a blood supply in the bioengineered meniscal tissue.