Ex vivo Expanded Erythroblast Transplantation (Autologous) for the treatment of patients with severe chronic limb ischemia (EVEETA study) : Phase I/II trial

2008 Fiscal Year Final Research Report

• Project/Area Number: 19590856
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Circulatory organs internal medicine
• Research Institution: Niigata University
• Principal Investigator: TOBA Ken Niigata University, 医歯学総合病院, 講師 (60313540)
• Co-Investigator(Kenkyū-buntansha): KATO Kiminori 新潟大学, 医歯学総合病院, 助教 (00303165) ; HANAWA Haruo 新潟大学, 医歯学系, 講師 (40282983) ; AIZAWA Yoshifuda 新潟大学, 医歯学系, 教授 (50143780)
• Project Period (FY): 2007 – 2008
• Keywords: 血管再生治療 / 重症下肢虚血 / 幹細胞培養法

Research Abstract

重症の下肢虚血患者に対して骨髄単核細胞移植による血管再生治療が行われてきたが、全身麻酔で大量の骨髄を採取する必要があり、また最重症例には無効であった.我々は骨髄中に含まれる未熟な赤血球系の細胞が血管再生を行うことを見つけた.少量の骨髄から大量の赤血球系の細胞を増幅培養する方法を開発した.この細胞が実際に強力な血管再生作用を持つことを動物実験で確認した.倫理委員会の承認を受けて5例の患者に治療を行った.目立った副作用はなく、また最重症例にも有効であった.今後は他の医療施設からも患者を引き受ける予定である.

Research Products

• [Journal Article] エリスロポエチン誘導体の血管新生作用 (2009)
  • Author(s): 鳥羽健, 小澤拓也, 相澤義房
  • Journal Title: Angiology Frontier 8 Pages: 61-69
• [Journal Article] 血管新生作用をもつエリスロポエチン誘導体 (2008)
  • Author(s): 鳥羽健
  • Journal Title: 医学のあゆみ 226 Pages: 1055-1060
• [Journal Article] 骨髄移植後の骨腫瘤形成性再発にリツキサン併用化学療法が有効であった急性リンパ性白血病 (2008)
  • Author(s): 阿部崇, 北嶋俊樹, 本間圭一郎, 倉崎桃里, 岡塚貴世志, 柴崎康彦, 桃井明仁, 黒羽高志, 増子正義, 八木沢久美子, 古川達雄, 鳥羽健, 相澤義房
  • Journal Title: 臨床血液 49 Pages: 1556-1561
  • Peer Reviewed
• [Journal Article] Plasmacytoid Dendritic Cell Leukemia with Potent Antigen-Presenting Ability (2008)
  • Author(s): Narita M, Kuroha T, Watanabe N, Hashimoto S, Tsuchiyama J, Tochiki N, Saitoh A, Satoh N, Furukawa T, Toba K, Fuse I, Aizawa Y, Takahashi M
  • Journal Title: Acta Haematology 120 Pages: 91-99
  • Peer Reviewed
• [Journal Article] Gene expression profiles of cardiomyocytes in rat autoimmune myocarditis by DNA microarray and increase of regenerating gene family (2008)
  • Author(s): Watanabe R, Hanawa H, Yoshida T, Ito M, Isoda M, Chang H, Toba K, Yoshida K, Kojima M, Otaki K, Ding L, Hao K Kato K, Kodama M, Aizawa Y
  • Journal Title: Transplantation Research 152 Pages: 119-127
  • Peer Reviewed
• [Journal Article] Imatinib mesilate inhibits neointimal hyperplasia via growth inhibition of vascular smooth muscle cells in a rat model of balloon injury (2008)
  • Author(s): Makiyama Y, Toba K, Kato K, Hirono S, Ozawa T, Saigawa T, Minagawa S, Isoda M, Asami F, Ikarashi N, Oda M, Moriyama M, Higashimura M, Kitajima T, Otaki K, Aizawa Y
  • Journal Title: Tohoku Journal of Experimental Medicine 215 Pages: 299-306
  • Peer Reviewed
• [Journal Article] Serum erythropoietin level as a marker of limb ischemia (2008)
  • Author(s): Ozawa T, Kato K, Toba K, Oda M, Saigawa T, Minagawa S, Makiyama Y, Isoda M, Higuchi M, Ikarashi N, Moriyama M, Higashimura M, Kitajima T, Otaki K, Hirono S, Okura Y, Hanawa H, Kodama M, Aizawa Y
  • Journal Title: International Journal of Cardiology 130 Pages: 106-108
  • Peer Reviewed
• [Journal Article] Anti-tumor cytotoxicity of gammadelta T cells expanded from peripheral blood cells of patients with myeloma and lymphoma (2008)
  • Author(s): Saitoh A, Narita M, Watanabe N, Tochiki N, Satoh N, Takizawa J, Furukawa T, Toba K, Aizawa Y, Shinada S, Takahashi M
  • Journal Title: Medical Oncology 25 Pages: 137-147
  • Peer Reviewed
• [Journal Article] Alteration of IL-17 related protein expression in experimental autoimmune myocarditis and inhibition of IL-17 by IL-10-Ig fusion gene transfer (2008)
  • Author(s): Chang H, Hanawa H, Yoshida T, Hayashi M, Liu H, Ding L, Otaki K, Hao K, Yoshida K, Kato K, Toba K, Kodama M, Maruyama H, Miyazaki J, Aizawa Y
  • Journal Title: Circulation Journal 72 Pages: 813-819
  • Peer Reviewed
• [Journal Article] Induction of recipient cell-specific donor T-cell anergy by UV-C-irradiated recipient immature monocyte-derived dendritic cells (2008)
  • Author(s): Tochiki N, Narita M, Zheng Z, Lu C, Saitoh A, Watanabe N, Satoh N, Furukawa T, Toba K, Fuse I, Aizawa Y, Takahashi M
  • Journal Title: Bone Marrow Transplantation 41 Pages: 1037-1045
  • Peer Reviewed
• [Journal Article] Temporal treatment with interferon-beta prevents hepatocellular carcinoma in hepatitis B virus-X gene transgenic mice (2008)
  • Author(s): Yamazaki K, Suzuki K, Ohkoshi S, Yano M, Kurita S, Aoki Y, Toba K, Takamura M, Yamagiwa S, Matsuda Y, Aoyagi Y
  • Journal Title: Journal of Hepatology 48 Pages: 255-265
  • Peer Reviewed
• [Journal Article] Prognostic factors for critical limb ischemia after autologous bone marrow implantation (2007)
  • Author(s): Oda M, Kato K, Toba K, Otaki K, Kitajima T, Ikarashi N, Yanagawa T, Higashimura M, Asami F, Isoda M, Ozawa T, Moriyama M, Hirono S, Okura Y, Hanawa H, Kodama M, Aizawa Y
  • Journal Title: Journal of Cardiology 50 Pages: 235-242
  • Peer Reviewed
• [Journal Article] エリスロポエチンを用いた循環器疾患治療 (2007)
  • Author(s): 加藤公則, 鳥羽健, 相澤義房
  • Journal Title: 呼吸と循環 55 Pages: 991-996
• [Journal Article] Enhancement of Anti-tumor Cytotoxicity of Expanded gammadelta T Cells by Stimulation with Monocyte-derived Dendritic Cells (2007)
  • Author(s): Saito A, Narita M, Yokoyama A, Watanabe N, Tochiki N, Satoh N, Takizawa J, Furukawa T, Toba K, Fuse I, Aizawa Y, Shinada S, Takahashi M
  • Journal Title: Journal of Clinical and Experimental Hematopathology 47 Pages: 61-72
  • Peer Reviewed
• [Journal Article] 血液細胞における細胞周期の解析法とその応用 (2007)
  • Author(s): 鳥羽健
  • Journal Title: 血液フロンティア 17 Pages: 1693-1702
• [Journal Article] Successful all-trans recinoic acid treatment of Acute Promyelocytic Leukemia with a rare variant NPM/RAR α translocation (2007)
  • Author(s): Okazuka K, Masuko M, Seki Y, Hama H, Honma N, Furukawa T, Toba K, Kishi K, Aizawa Y
  • Journal Title: International Journal of Hematology 86 Pages: 246-249
  • Peer Reviewed
• [Journal Article] Risk factors for acute graft-versus-host disease after allogeneic hematopoietic stem cell transplantation : retrospective analysis of 73 patients who received cyclosporin A (2007)
  • Author(s): Izumi N, Furukawa T, Sato N, Okazuka K, Tsukada N, Abe T, Yano T, Kurasaki T, Masuko M, Toba K, Takahashi M, Aizawa Y
  • Journal Title: Bone Marrow Transplantation 40 Pages: 875-880
  • Peer Reviewed
• [Journal Article] Identification of an overexpressed gene, HSPA4L, the product of which can provoke prevalent humoral immune responses in leukemia patients (2007)
  • Author(s): Takahashi H, Furukawa T, Yano T, Sato N, Takizawa J, Kurasaki T, Abe T, Narita M, Masuko M, Koyama S, Toba K, Takahashi M, Aizawa Y
  • Journal Title: Experimental Hematology 35 Pages: 1091-1099
  • Peer Reviewed
• [Journal Article] Plasma brain natriuretic peptide during myeloablative stem cell transplantation (2007)
  • Author(s): Masuko M, Ito M, Kurasaki T, Yano T, Takizawa J, Toba K, Aoki S, Fuse I, Kodama M, Furukawa T, Aizawa Y
  • Journal Title: Internal Medicine 46 Pages: 551-555
  • Peer Reviewed
• [Presentation] Evaluation of the Prospective Observation of erythropoietin-administration for the treatment of Acute Myocardial Infarction (EPO-AMI) (2009)
  • Author(s): Suzuki H, Kato K, Ozawa T, Toba K, Akutsu Y, Iso Y, Kobayashi Y, Takeyama Y, Kobayashi N, Yokoyama S, Fukuda N, Akazawa K, Aizawa Y
  • Organizer: 第73回日本循環器学会総会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-03-21
• [Presentation] The effects of erythropoietin-derivatives on monocrotaline-induced pulmonary hypertension in rats (2009)
  • Author(s): Ikarashi N, Toba K, Kato K, Takayama T, Oda M, Ohtaki K, Yanagawa T, Asami F, Ozawa T, Hanawa H, Kodama M, Aizawa Y
  • Organizer: 第73回日本循環器学会総会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-03-21
• [Presentation] Phase I/II clinical study of angiogenesis by Ex-Vivo Expanded Erythroblast transplantation (Autologous) (EVEETA) for the treatment of patients with chronic severe limb ischemia (2009)
  • Author(s): Ozawa T, Oda M, Toba K, Kato K, Takayama T,Yanagawa T, Ikarashi N, Asami F, Hanawa H, Aizawa Y.
  • Organizer: 第73回日本循環器学会総会学術集会
  • Place of Presentation: 大阪国際会議場
  • Year and Date: 2009-03-21
• [Presentation] シンポジウム5重症下肢虚血の治療、最前線. 赤芽球の血管新生作用と臨床への応用 (2008)
  • Author(s): 鳥羽健, 加藤公則
  • Organizer: 第14回日本血管内治療学会総会
  • Place of Presentation: アルカディア市ヶ谷
  • Year and Date: 2008-07-25
• [Presentation] Human osteoblast as well as mesenchymal stem cells suppress allogeneic T cells (2008)
  • Author(s): Kitajima T, Masuko M, Kurasaki T, Shibasaki Y, Furukawa T, Toba K, Aizawa Y
  • Organizer: International Society for Experimental Hematology
  • Place of Presentation: Renaissance Boston Waterfront Hotel
  • Year and Date: 2008-07-10
• [Presentation] Intravenous erythropoietin administration attenuated monocrotaline-induced rat pulmonary hypertension (2008)
  • Author(s): Ikarashi N, Kato K, Toba K, Takayama T, Oda M, Otaki K, Yanagawa T, Asami F, Ozawa T, Hanawa H, Kodama M, Aizawa Y
  • Organizer: 第72回日本循環器学会総会学術集会
  • Place of Presentation: アクロス福岡
  • Year and Date: 2008-03-30
• [Presentation] Ex vivo expanded erythroblast-transplantation (Autologous) therapy, EVEETA, a novel remedy for severe limb ischemia (2008)
  • Author(s): Oda M, Kato K, Toba K, Takayama T, Ohtaki K, Yanagawa T, Ikarashi N, Asami F, Ozawa T, Hirono S, Hanawa H, Aizawa Y
  • Organizer: 第72回日本循環器学会総会学術集会
  • Place of Presentation: アクロス福岡
  • Year and Date: 2008-03-30
• [Remarks]
  • URL: http://www.med.niigata-u.ac.jp/in1/godoproject/saisei.html