Cell Therapy for Angiogenesis

“ Alone we can do so little; together we can do so much.” — —Helen Keller Therapeutic angiogenesis remains a worthy but somewhat elusive clinical goal. Attempts to increase blood flow to ischemic tissue have included a variety of physical and biological approaches. A growing understanding of the cells and proteins involved in vessel sprouting and maturation led to a number of genetic approaches aimed at promoting angiogenesis in ischemic myocardium and skeletal muscle. In spite of several strategies undergoing testing in clinical trials, the delivery of vectors encoding for single growth factors has not yet shown clinical efficacy. In response to these challenges, a number of groups have aimed to provide multiple angiogenic factors for ischemic tissue. These approaches include gene transfer of transcription factors that regulate multiple angiogenic peptides (such as hypoxia inducible factor-1α) or transplantation of cells capable of providing a regulated source of secreted growth factors and cytokines. A potential advantage of delivered cells is that they may also directly participate in new vessel formation. The article by Yoon and Hur1 in this issue of Circulation extends this approach by testing the synergistic effects of delivering 2 types of circulation-derived cells capable of participating in the angiogenic process. As such, this article reflects the potential of coordinated combination biological approaches for angiogenesis.See p 1618 The angiogenic effects of cell delivery were originally demonstrated by Asahara et al2,3 using circulation-derived cells that were capable of assuming features of endothelial cells after brief periods of in vitro culture. These cells were referred to as endothelial progenitor cells (EPCs). This approach has been tested by Assmus and colleagues in the Transplantation of Progenitor Cells and Regeneration Enhancement in Acute Myocardial Infarction (TOPCARE-AMI) study with intracoronary delivery of EPCs into the infarct-related coronary artery of patients after …