Bone marrow mononuclear cells stimulate angiogenesis when transplanted into surgically induced fibrocollagenous tunnels: results from a canine ischemic hindlimb model.

Abstract

Progenitor cell transplantation has been considered as a potential angiogenesis therapy for the ischemic hindlimb. In this work we performed an ischemic hindlimb model in dogs. We ligated the middle sacra and the external right iliac arteries. After 7 days, the femoral artery was ligated and removed, and three Silastic tubes were inserted into the gracilis muscle to create fibrocollagenous tunnels. After Silastic implantation, we administered saline or granulocyte colony stimulating factor (G-CSF) subcutaneously daily during 5 days. Fourteen days after device positioning we transplanted bone marrow mononuclear cells (BMMC) into the tunnels previously formed by Silastic tube reaction. Twenty-eight days later, contrasted angiographies were performed and angiographic scores were calculated. Also, vessels and endothelial cells and proliferating cells were identified by immunochemistry of muscle sections. Results demonstrated that BMMC transplantation enriched by G-CSF administration significantly stimulates angiogenesis in the ischemic hindlimb, and more than BMMC transplantation alone. Transplantation of progenitor cells in an appropriate extracellular matrix is a potential therapy for hindlimb ischemia.