Cell-Based Therapies for Peripheral Arterial DiseaseYasuyuki Fujita and Atsuhiko Kawamoto*
Division of Vascular Regeneration, Unit of Regenerative Medicine, Institute of Biomedical Research and Innovation, Kobe, Japan
- *Corresponding Author:
- Atsuhiko Kawamoto, M.D., Ph.D
Division of Vascular Regeneration, Unit of Regenerative Medicine
Institute of Biomedical Research and Innovation
2-2 Minatojima-Minamimachi, Chuo-Ku, Kobe 650-0047, Japan
E-mail: [email protected]
Received date: July 23, 2014; Accepted date: September 15, 2014; Published date: September 17, 2014
Citation: Fujita Y, Kawamoto A (2014) Cell-Based Therapies for Peripheral Arterial Disease. J Stem Cell Res Ther 4:234. doi:10.4172/2157-7633.1000234
Copyright: © 2014 Fujita Y, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Chronic critical limb ischemia (CLI) is defined as the end-stage of lower limb ischemia due to atherosclerotic peripheral arterial disease (PAD) or vasculitis including thromboangitis obliterance (Buerger’s disease). CLI patients are at very high risk of amputation and experience poor physical function, leading to severe morbidity and mortality despite the development of surgical bypass technique or endovascular approach. Therefore, exploring novel strategies for blood flow recovery of ischemic limbs is urgently needed for patients with CLI. Although researchers initially focused on gene therapy using proangiogenic growth factors, recent discovery of somatic stem/progenitor cells including bone marrow (BM)-derived endothelial progenitor cells (EPCs) and mesenchymal stem cells (MSCs) has drastically developed the field of therapeutic angiogenesis for CLI. In 2002, the first clinical trial of intramuscular injection of BM-derived mononuclear cells (BM-MNCs) demonstrated safety, feasibility and efficacy for CLI patients. Since then, at least 50 clinical trials of BM- and peripheral blood (PB)-derived MNC therapy, 4 trials of CD34+ cell (an EPC-enriched fraction) therapy and 8 trials of MSC therapy have been performed for CLI. Overall, the results of these early phase clinical trials regarding stem/progenitor cell therapies may be safe, feasible and effective. However, only few late-phase clinical trials have been conducted. Currently, at least 3 phase III trials including 2 trials using BMMNCs and 1 trial using granulocyte-colony stimulating factor (G-CSF)-mobilized PB-MNCs are ongoing. This review provides an overview of the preclinical and clinical reports to demonstrate the usefulness and the current limitations of the cell-based therapies.