Peripheral Blood Mononuclear Cells for Limb Ischemia
There is accumulating evidence that the peripheral blood is a source of pro-angiogenic mononuclear cells (MNCs). These cells were initially described as endothelial progenitor cells (EPCs) expressing CD34 and vascular endothelial growth factor (VEGF) rece
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Peripheral Blood Mononuclear Cells for Limb Ischemia Masayoshi Suda†, Ippei Shimizu†, Yohko Yoshida, and Tohru Minamino
Abstract There is accumulating evidence that the peripheral blood is a source of pro-angiogenic mononuclear cells (MNCs). These cells were initially described as endothelial progenitor cells (EPCs) expressing CD34 and vascular endothelial growth factor (VEGF) receptor 2. Pro-angiogenic MNCs are now known to represent a mixed population of cells, including hematopoietic stem cells, mesenchymal stem cells, and EPCs. The therapeutic potential of bone marrow or peripheral blood MNCs has been tested in patients with severe peripheral artery disease, showing that implanted cells promote the production of pro-angiogenic molecules in an autocrine and/or paracrine fashion and contribute to the recovery of blood flow in ischemic limbs. The molecular mechanisms underlying therapeutic angiogenesis are yet to be defined, but a number of studies have indicated that injection of either bone marrow or peripheral blood MNCs improves the clinical outcome in patients with severe limb ischemia and importantly achieves this effect with minor adverse events. In addition to controlling classical risk factors such as diabetes and/or hypertension, recent studies have suggested several combination therapies that can contribute to improving the therapeutic effects of these pro-angiogenic cells. Therapeutic angiogenesis promoted by the injection of autologous peripheral blood MNCs is an essential and practical treatment for patients who have no other options. Keywords Therapeutic angiogenesis • Peripheral blood mononuclear cells • Endothelial progenitor cells • Cell transplantation • Limb ischemia
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Masayoshi Suda and Ippei Shimizu contributed equally to this work.
M. Suda • T. Minamino, M.D., Ph.D. (*) Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8510, Japan e-mail: [email protected] I. Shimizu • Y. Yoshida Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuo-ku, Niigata 951-8510, Japan Division of Molecular Aging and Cell Biology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan © Springer Nature Singapore Pte Ltd. 2017 Y. Higashi, T. Murohara (eds.), Therapeutic Angiogenesis, DOI 10.1007/978-981-10-2744-4_3
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3.1 Introduction The prevalence of peripheral artery disease (PAD) continues to increase. The clinical outcome of critical limb ischemia remains poor, especially in the setting of limb amputation, and it is an urgent task to develop new therapies for this condition. Induction of angiogenic proteins such as vascular endothelial growth factor (VEGF) or fibroblast growth factor (FGF) contributed significantly to restoring the perfusion of ischemic limbs in preclinical studies performed in rodents. However, clinical studies designed to assess the au
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