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Peripheral Blood Mononuclear Cells for Limb Ischemia

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Therapeutic Angiogenesis

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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.

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Acknowledgments

This work was supported by a Grant-in-Aid for Scientific Research, a Grant-in-Aid for Scientific Research on Innovative Areas (Stem Cell Aging and Disease), and a Grant-in-Aid for Exploratory Research from the Ministry of Education, Culture, Sports, Science and Technology (MEXT) of Japan and grants from the Takeda Medical Research Foundation, the Japan Diabetes Foundation, the Ono Medical Research Foundation, the Daiichi Sankyo Foundation of Life Science, the Japan Foundation for Applied Enzymology, the Takeda Science Foundation, the SENSHIN Medical Research Foundation, and the Terumo Foundation (to T.M.); by a Grants-in-Aid for Young Scientists (Start-up) (JSPS KAKENHI, Grant Number 26893080) and grants from the Uehara Memorial Foundation, Takeda Science Foundation, Kowa Life Science Foundation, Manpei Suzuki Diabetes Foundation, Kanae Foundation, Japan Heart Foundation Research Grant, the Senri Life Science Foundation, SENSHIN Medical Research Foundation, ONO Medical Research Foundation, Tsukada Grant for Niigata University Medical Research, the Nakajima Foundation, SUZUKEN Memorial Foundation, HOKUTO Corporation, Inamori Foundation, Mochida Memorial Foundation for Medical and Pharmaceutical Research, Banyu Foundation Research Grant, Grant for Basic Science Research Projects from The Sumitomo Foundation, and Grants-in-Aid for Encouragement of Young Scientists (A) (JSPS KAKENHI Grant Number 16H06244) (to I.S.); by a Grants-in-Aid for Encouragement of Young Scientists (B) (JSPS KAKENHI Grant Number 16K19531), Japan Heart Foundation, Dr. Hiroshi Irisawa & Dr. Aya Irisawa Memorial Research Grant, SENSHIN Medical Research Foundation grant, SUZUKEN Memorial Foundation, Takeda Science Foundation, ONO Medical Research Foundation, Uehara Memorial Foundation, and Research Foundation for Community Medicine (to Y.Y.); and by a Grant-in-Aid for Scientific Research (C) (JSPS KAKENHI Grant Number 15K09154) (to M.S.) and by a grant from Bourbon (to T.M., I.S., and Y.Y.).

Disclosures

M.S., I.S., Y.Y., and T.M. disclose no conflict of interest.

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Author notes

  1. Masayoshi Suda and Ippei Shimizu contributed equally to this work.

Authors and Affiliations

  1. Department of Cardiovascular Biology and Medicine, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachidori, Chuo-ku, Niigata, 951-8510, Japan

    Masayoshi Suda, Ippei Shimizu, Yohko Yoshida & Tohru Minamino M.D., Ph.D.

  2. Division of Molecular Aging and Cell Biology, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan

    Ippei Shimizu & Yohko Yoshida

Authors
  1. Masayoshi Suda
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  2. Ippei Shimizu
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  3. Yohko Yoshida
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  4. Tohru Minamino M.D., Ph.D.
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Corresponding author

Correspondence to Tohru Minamino M.D., Ph.D. .

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Editors and Affiliations

  1. Research Institute for Radiation Biology and Medicine, Hiroshima University, Hiroshima, Japan

    Yukihito Higashi

  2. Department of Cardiology, Nagoya University, Aichi, Japan

    Toyoaki Murohara

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Suda, M., Shimizu, I., Yoshida, Y., Minamino, T. (2017). Peripheral Blood Mononuclear Cells for Limb Ischemia. In: Higashi, Y., Murohara, T. (eds) Therapeutic Angiogenesis. Springer, Singapore. https://doi.org/10.1007/978-981-10-2744-4_3

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  • DOI: https://doi.org/10.1007/978-981-10-2744-4_3

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