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BioMed Research International
Volume 2013, Article ID 186215, 8 pages
Review Article

Gene Therapy and Cell-Based Therapies for Therapeutic Angiogenesis in Peripheral Artery Disease

1Division of Vascular Medicine and Epigenetics, Department of Child Development, United Graduate School of Child Development, Osaka University, Kanazawa University, and Hamamatsu University School of Medicine, 2-1 Yamadaoka, Suita 565-0817, Osaka, Japan
2Department of Clinical Gene Therapy, Graduate School of Medicine, Osaka University, 2-2 Yamadaoka, Suita 565-0871, Osaka, Japan

Received 16 August 2013; Accepted 9 September 2013

Academic Editor: Ken Suzuki

Copyright © 2013 Munehisa Shimamura et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


Gene therapy and cell-based therapy have emerged as novel therapies to promote therapeutic angiogenesis in critical limb ischemia (CLI) caused by peripheral artery disease (PAD). Although researchers initially focused on gene therapy using proangiogenic factors, such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), and hepatocyte growth factors (HGF), cell therapy using bone marrow mononuclear cells (BMMNCs), mesenchymal stem cells (BMMSCs), G-CSF-mobilized peripheral blood mononuclear cells (M-PBMNCs), and endothelial progenitor cells (EPCs) have also been extensively studied. Based on the elaborate studies and favorable results of basic research, some clinical phase I/II trials have been performed, and the results demonstrate the safety of these approaches and their potential for symptomatic improvement in CLI. However, the phase 3 clinical trials have thus far been limited to gene therapy using the HGF gene. Further studies using well-designed larger placebo-controlled and long-term randomized control trials (RCTs) will clarify the effectiveness of gene therapy and cell-based therapy for the treatment of CLI. Furthermore, the development of efficient gene transfer systems and effective methods for keeping transplanted cells healthy will make these novel therapies more effective and ease the symptoms of CLI.