Heart and Vessels

, Volume 27, Issue 1, pp 38–45

Hypocellularity and insufficient expression of angiogenic factors in implanted autologous bone marrow in patients with chronic critical limb ischemia

  • Masato Oda
  • Ken Toba
  • Kiminori Kato
  • Takuya Ozawa
  • Takao Yanagawa
  • Noboru Ikarashi
  • Tsugumi Takayama
  • Tomoyasu Suzuki
  • Haruo Hanawa
  • Masayoshi Masuko
  • Hironori Kobayashi
  • Yoshifusa Aizawa
Original Article

DOI: 10.1007/s00380-011-0125-5

Cite this article as:
Oda, M., Toba, K., Kato, K. et al. Heart Vessels (2012) 27: 38. doi:10.1007/s00380-011-0125-5

Abstract

The aim of this study was to identify the clinical parameters of absolutely poor-prognosis patients with chronic critical limb ischemia (AP-CLI). Sixteen no-option CLI patients with arteriosclerosis obliterans: ASO (nine) and non-ASO patients (seven) treated with bone marrow-mononuclear cell implantation (BMI) were analyzed. There were three AP-CLI patients (all ASO). The mRNA expression of several angiogenic factors in the implanted cells was analyzed in comparison with normal donor bone marrow. To observe the response of bone marrow components to hypoxia, normal bone marrow cells were cultured for 24 h in 2.5% O2, and mRNA expression of angiogenic factors were measured. AP-CLI patients exhibited extraordinary low bone marrow cellularity as well as the percentage of CD34-positive cells. Among angiogenic factors, only VEGF expression was maintained in response to HIF-1, while other factors such as HGF, Ang-1, PLGF, and SDF-1 decreased in the implanted bone marrow cells of the patients with CLI compared to normal bone marrow cells. HIF-1 and all of the five angiogenic factors increased in vitro in response to hypoxia. Thus it is highly likely that angiogenic factors except VEGF do not respond to chronic ischemia in bone marrow in vivo. An organ-protection system against tissue ischemia may be applied for acute hypoxia, but it may be insufficient for chronic ischemia.

Keywords

Critical limb ischemia Bone marrow implantation Angiogenic factors Hypoxia 

Copyright information

© Springer 2011

Authors and Affiliations

  • Masato Oda
    • 1
  • Ken Toba
    • 1
    • 2
  • Kiminori Kato
    • 1
  • Takuya Ozawa
    • 1
  • Takao Yanagawa
    • 1
  • Noboru Ikarashi
    • 1
  • Tsugumi Takayama
    • 1
  • Tomoyasu Suzuki
    • 1
  • Haruo Hanawa
    • 1
  • Masayoshi Masuko
    • 1
  • Hironori Kobayashi
    • 1
  • Yoshifusa Aizawa
    • 1
  1. 1.First Department of Internal MedicineNiigata University Medical and Dental HospitalNiigataJapan
  2. 2.Division of HematologyNiigata University Graduate School of Medical and Dental SciencesNiigataJapan

Personalised recommendations