Clinical features and predictors of patients with critical limb ischemia who responded to autologous mononuclear cell transplantation for therapeutic angiogenesis
- 247 Downloads
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.
KeywordsCritical 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.
- 10.Matoba S, Tatsumi T, Murohara T, Imaizumi T, Katsuda Y, Ito M, Saito Y, Uemura S, Suzuki H, Fukumoto S, Yamamoto Y, Onodera R, Teramukai S, Fukushima M, Matsubara H, TACT Follow-up Study Investigators (2008) Long-term clinical outcome after intramuscular implantation of bone marrow mononuclear cells (Therapeutic Angiogenesis by Cell Transplantation [TACT] trial) in patients with chronic limb ischemia. Am Heart J 156:1010–1018.CrossRefPubMedGoogle Scholar
- 11.Tateno K, Minamino T, Toko H, Akazawa H, Shimizu N, Takeda S, Kunieda T, Miyauchi H, Oyama T, Matsuura K, Nishi J, Kobayashi Y, Nagai T, Kuwabara Y, Iwakura Y, Nomura F, Saito Y, Komuro I (2006) Critical roles of muscle-secreted angiogenic factors in therapeutic neovascularization. Circ Res 98:1194–1202CrossRefPubMedGoogle Scholar
- 20.Saigawa T, Kato K, Ozawa T, Toba K, Makiyama Y, Minagawa S, Hashimoto S, Furukawa T, Nakamura Y, Hanawa H, Kodama M, Yoshimura N, Fujiwara H, Namura O, Sogawa M, Hayashi J, Aizawa Y (2004) Clinical application of bone marrow implantation in patients with arteriosclerosis obliterans, and the association between efficacy and the number of implanted bone marrow cells. Circ J 68:1189–1193CrossRefGoogle Scholar
- 21.Iso Y, Soda T, Sato T, Sato R, Kusuyama T, Omori Y, Shoji M, Koba S, Katagiri T, Kobayashi Y, Suzuki H (2010) Impact of implanted bone marrow progenitor cell composition on limb salvage after cell implantation in patients with critical limb ischemia. Atherosclerosis 209:167–172CrossRefPubMedGoogle Scholar
- 22.Horie T, Onodera R, Akamastu M, Ichikawa Y, Hoshino J, Kaneko E, Iwashita C, Ishida A, Tsukamoto T, Teramukai S, Fukushima M, Kawamura A, Japan Study Group of Peripheral Vascular Regeneration Cell Therapy (JPRCT) (2010) Long-term clinical outcomes for patients with lower limb ischemia implanted with G-CSF-mobilized autologous peripheral blood mononuclear cells. Atherosclerosis 208:461–466CrossRefPubMedGoogle Scholar
- 24.Saito Y, Sasaki K, Katsuda Y, Murohara T, Takeshita Y, Okazaki T, Arima K, Katsuki Y, Shintani S, Shimada T, Akashi H, Ikeda H, Imaizumi T (2007) Effect of autologous bone-marrow cell transplantation on ischemic ulcer in patients with Buerger’s disease. Circ J 71:1187–1192CrossRefPubMedGoogle Scholar