Induction of Angiogenesis In Tissue Engineered Scaffolds for Bone Repair: A Combined Gene Therapy-Cell Transplantation Approach

One of the fundamental principles underlying tissue engineering approaches is that newly formed tissue must maintain sufficient vascularization to support its growth. Efforts to induce vascular growth into tissue engineered scaffolds have recently been dedicated to developing novel strategies to deliver specific biological factors that direct the recruitment of endothelial cell (EC) progenitors, and their differentiation. The challenge, however, lies in orchestration of the cells, appropriate biological factors and optimal factor doses. This study reports a novel approach as a step forward to resolve this dilemma by combining an ex-vivo gene transfer strategy and EC transplantation. The utility of this approach was evaluated using three dimensional (3-D) poly(lactide-co-glycolide) (PLAGA) sintered microsphere scaffolds for bone tissue engineering applications. Our goal was achieved by isolation and transfection of adipose derived stromal cells (ADSCs) with adenovirus encoding the cDNA of vascular endothelial growth factor (VEGF). We demonstrated that the combination of VEGF releasing ADSCs and ECs results in marked vascular growth within PLAGA scaffolds. We, thereby, delineate the potential of ADSCs to promote vascular growth into biomaterials.