Hobo K et al. (2008) Therapeutic angiogenesis using tissue engineered human smooth muscle cell sheets. Arterioscler Thromb Vasc Biol 28: 637–643

Surgical and percutaneous interventions for peripheral arterial disease only treat focal lesions, and do not reduce atherosclerosis, causing restenosis, and disease recurrence at other sites. The induction of angiogenesis is, therefore, desirable in the treatment of this disease. Some studies have suggested that therapeutic angiogenesis can be achieved through the administration of specific growth factors or the transplantation of isolated cells. However, these strategies have shown limited success; effective revascularization might require administration of multiple growth factors. Outcomes could be improved by transplantation of cell sheets, which can be applied to target lesions without becoming isolated from neighboring cells, and which might secrete more growth factors than isolated cells.

In a Japanese study, Hobo and colleagues investigated the effect of transplanted tissue-engineered cell sheets on blood-vessel formation and functional recovery in athymic rats with limb ischemia. The rats were divided into three groups and received either xenografts of human smooth-muscle-cell sheet or fibroblast-cell sheet, or were untreated controls. All rats were monitored for 21 days. Significant improvements in perfusion were observed in the treatment groups compared with the control group throughout the study period. Smooth-muscle cells achieved the greatest improvement and were associated with development of mature capillary networks. In vitro, both cell types secreted proangiogenic growth factors that stimulate blood vessel formation, with the greatest potency observed in smooth-muscle cells.

The authors explain that the transplanted smooth-muscle cells induced neovascularization by localized secretion of proangiogenic growth factors and by migration into ischemic tissues, where they became incorporated into new blood vessels.