Recent progress in therapeutic angiogenesis

Coronary artery disease and peripheral arterial disease are devastating status of acute vessel occlusion in diseased vessels that are already narrowed enough by atherosclerotic process. People are now focused on therapeutic angiogenesis against the ischemic diseases, to supply and growth of new vessels into the ischemic tissue. Recently, we and others performed autologous transplantation of bone marrow mononuclear cell or endothelial progenitor cell and gene therapy using hepatocyte growth factor (HGF) in clinical trials. Autologous implantation of bone marrow mononuclear cells or endothelial progenitor cells in ischemic limb or heart may induce blood flow and improve function in several pilot clinical studies. The regenerative potential of bone-marrow cells can be explained by any of four mechanisms, transdiffentiaion, cytokine-induced growth, stimulation of endogenous stem cells, and induction of cell fusion. Transdifferentiaion has been described by previous investigators and the concept has been called into question by recent experimental studies. In the pilot clinical study, similar improvements were seen in gene therapy using HGF in peripheral arterial diseases which might be more noninvasive. The clinical significance of the novel therapeutic approach might embrace the large number of patients with peripheral arterial diseases and with chronic coronary artery disease. And we need to figure out the strong angiogenic factor or specific differentiated progenitor cells for therapeutic angiogenesis in the study of bone marrow cell therapy. For the patients, we need to constitute a safe and effective strategy for achievement of therapeutic angiogenesis.