Heart and Vessels

, Volume 32, Issue 9, pp 1099–1108 | Cite as

Clinical features and predictors of patients with critical limb ischemia who responded to autologous mononuclear cell transplantation for therapeutic angiogenesis

  • Naoyoshi Aoyama
  • Makoto Nishinari
  • Shinichi Ohtani
  • Akifumi Kanai
  • Chiharu Noda
  • Mitsuhiro Hirata
  • Akira Miyamoto
  • Masafumi Watanabe
  • Tohru Minamino
  • Tohru Izumi
  • Jyunya Ako
Original Article


The clinical features of patients with critical limb ischemia (CLI) who responded to angiogenesis using autologous peripheral blood mononuclear cell transplantation (PB-MNC) have not yet been fully characterized, and there are no useful predictors to judge the curative effect in the early period after PB-MNC. This study sought to clarify the clinical features and predictors in patients with CLI who were successfully treated using PB-MNC. 30 consecutive patients [arteriosclerosis obliterans: 24 patients, thromboangiitis obliterans: 6 patients] who were diagnosed with major amputation despite maximal medical therapy were enrolled in this study. The study endpoint was major amputation within 3 months after PB-MNC. The collected data were evaluated for correlation between patients with and without major amputation within 3 months after PB-MNC. Six patients underwent major amputation and 1 patient underwent minor amputation. In the patients with major amputation, transcutaneous oxygen tension before PB-MNC and transplanted CD34-positive cells were lower than those of patients without major amputation. In the patients with amputation, interleukin-6 (IL-6) continued to increase after the first PB-MNC, and basic fibroblast growth factor (bFGF) decreased within 3 days after the first PB-MNC. PB-MNC was useful for the patients who were managed for inflammation and who had revascularization of the upper-popliteal arteries and two of the infra-popliteal arteries by endovascular and/or surgical revascularization. Variation in IL-6 and bFGF in the early period after PB-MNC could be useful predictors for the requirement of amputation within 3 months after PB-MNC.


Critical limb ischemia (CLI) Autologous peripheral blood mononuclear cell transplantation (PB-MNC) Therapeutic angiogenesis Arteriosclerosis obliterans (ASO) Thromboangiitis obliterans (TAO) Peripheral arterial disease (PAD) 



We express our thanks to the members of Cardiovascular Center, Blood Transfusion Department, and Department of Dolorology, Kitasato University Hospital, for their kind assistance and many helpful suggestions. We also express our sincere gratitude to our irreplaceable colleagues, scientific officer Kazuyo Yagi in Blood Transfusion Department and scientific officer Kazumi Nakazato in Department of Cardiovascular Medicine, for their contribution to this study.

Compliance with ethical standards

Conflict of interest

The authors declare no conflicts of interests in this study.


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Copyright information

© Springer Japan 2017

Authors and Affiliations

  • Naoyoshi Aoyama
    • 1
  • Makoto Nishinari
    • 2
  • Shinichi Ohtani
    • 3
  • Akifumi Kanai
    • 4
  • Chiharu Noda
    • 2
  • Mitsuhiro Hirata
    • 5
  • Akira Miyamoto
    • 6
  • Masafumi Watanabe
    • 7
  • Tohru Minamino
    • 8
  • Tohru Izumi
    • 9
  • Jyunya Ako
    • 2
  1. 1.Division of Internal and Emergency Medicine, Department of Comprehensive MedicineResearch and Development Center for New Medical Frontiers, Kitasato University School of MedicineSagamiharaJapan
  2. 2.Department of Cardiovascular MedicineKitasato University School of MedicineSagamiharaJapan
  3. 3.Department of Transfusion Medicine and Cell TransplantationKitasato University School of MedicineSagamiharaJapan
  4. 4.Division of Dolorology, Department of Comprehensive MedicineResearch and Development Center for New Medical Frontiers, Kitasato University School of MedicineSagamiharaJapan
  5. 5.Division of Surgical Operation Management, Department of Comprehensive MedicineResearch and Development Center for New Medical Frontiers, Kitasato University School of MedicineSagamiharaJapan
  6. 6.Cardiology DepartmentCardiovascular Center, Takatsu General HospitalKawasakiJapan
  7. 7.Department of Cardiovascular MedicineUniversity of Tokyo HospitalTokyoJapan
  8. 8.Department of Cardiovascular Biology and MedicineNiigata University Graduate School of Medical and Dental SciencesNiigataJapan
  9. 9.Niigata Minami HospitalNiigataJapan

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