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Therapeutic angiogenesis by transplantation of bone marrow stem cells

Therapeutic angiogenesis by transplantation of bone marrow stem cells
通过骨髓干细胞移植进行治疗性血管生成
批准号:
13470152
负责人:
MATSUBARA Hiroaki
金额:
$10.24万
依托单位:
依托单位国家:
日本
项目类别:
Grant-in-Aid for Scientific Research (B)
财政年份:
2001
资助国家:
日本
项目状态:
已结题
起止时间:
2001 至 2002

项目摘要

项目成果

MATSUBARA Hiroaki的其他基金

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相关文献

中文摘要
翻译
通过多中心研究(act -1研究组),在103例肢体缺血患者中建立了自体骨髓单个核细胞(BM-MNC)的治疗性血管生成。安全性和有效性通过2年随访研究(22例)获得批准。CD34^+细胞表达bFGF>>VEGF>血管生成素-1,而CD34^+细胞主要表达其受体。在bm - mnc植入的肢体中,踝关节-肱压力指数(ABI)从基线的0.57增加到第4周的0.66和第24周的0.64 (P<0.0001)。84例患者中有70例缺血肢体的静息疼痛得到缓解,疼痛受限的跑步机行走时间显著改善(从基线时的1.4分钟到第4周时的3.6分钟和第24周时的4.2分钟,P<0.0001)。73条肢体中54条的缺血性溃疡或坏疽愈合,包括成功的肢体保留。免疫组织化学分析显示Ki-67阳性增殖内皮细胞新毛细血管形成显著增加。基于act -1研究的结果和猪模型的临床前实验,我们对3例无选择的缺血性冬眠心肌患者(n=3)进行了单细胞移植术的临床试验。取BM-MNC 0.2 ml,用27G针经导管注入20个不同部位(共1 × 10^8个细胞)。心绞痛发生率显著降低,局部灌注缺血区壁运动改善(SPECT、NOGA心室造影)。每月24小时动态心电图记录1年半无明显心律失常。因此,基于细胞的研究性治疗缺血性心脏病被证明是安全可行的。
英文摘要
Therapeutic angiogenesis by transplantation of autologous bone marrow mononuclear cells(BM-MNC) was established in 103 patients with ischemic limbs by multi-center study(TACT-1 Study Group) in Japan. Safety and efficacy was approved with 2-year follow-up study(22 patients). CD34^+ cells expressed bFGF>>VEGF>angiopoietin-1, while CD34^+ cells predominantly expressed their receptors. In BM-MNC-implanted limbs, ankle-brachial pressure index(ABI) was increased from 0.57 at baseline to 0.66 at week 4 and 0.64 at week 24 (P<0.0001). Rest pain in ischemic limbs was regressed in 70 of 84 patients, and their pain-limited treadmill walking time was significantly improved(from 1.4 min at baseline to 3.6 at week 4 and 4.2 at week 24,P<0.0001). Ischemic ulcers or gangrenes were healed in 54 of 73 limbs including successful limb salvage. Immunohistochemical analysis revealed a striking increase in new capillary formation with Ki-67 positive proliferating endothelial cells. On basis of the results of TACT-1 Study and pre-clinical experiments using porcine models, we performed the clinical trial of a sole cell therapy using catheter-based BM-MNC implantation in three no-option patients(n=3) with ischemic hibernating myocardium. 0.2 ml of BM-MNC was injected into 20 different sites(total 1x10^8 cells) via catheter with a 27G needle. Angina occurrence decreased dramatically and improvement in wall motion was observed in ischemic area with regional perfusion(SPECT, NOGA ventriography). There was no substantial arrhythmia on 24 h Holter recordings performed monthly for 1.5 year. Thus, cell-based investigational therapies for ischemic heart diseases were shown to be safe and feasible.
期刊论文(46)
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科研奖励(0)
会议论文
Yang Z, Matsubara H, 他7名: "Angiotensin II type 2 receptor overexpression preserves left ventricular function after myocardial infarction."Circulation. 106. 106-111 (2002)
Yang Z、Matsubara H 和其他 7 人:“血管紧张素 II 2 型受体过度表达可保护心肌梗塞后的左心室功能。”Circulation。106. 106-111 (2002)
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通讯作者:
Tateishi-Yuyama E, Matsubara H, Murohara T, Ikeda U, Shintani S, Masaki H, Shimada K, Iwasaka T, Imaizumi T: "Therapeutic angiogenesis for patients with limb ischemia by autologous transplantation of bone marrow cells : a pilot study and a randomised cont
Tateishi-Yuyama E、Matsubara H、Murohara T、Ikeda U、Shintani S、Masaki H、Shimada K、Iwasaka T、Imaizumi T:“通过自体骨髓细胞移植治疗肢体缺血患者的血管生成:一项初步研究和
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Fujiyama S, Amano K, Matsubara H., 他6人: "Bone Marrow Monocyte Lineage Cells Adhere on Injured Endothelium in a Monocyte Chemoattractant Protein-1-Dependent Manner and Accelerate Reendothelializaion as Endothelial Progenitor Cells"Circ Res. 93. 980-989 (20
Fujiyama S、Amano K、Matsubara H. 和其他 6 人:“骨髓单核细胞谱系细胞以单核细胞趋化蛋白 1 依赖性方式粘附在受损的内皮细胞上并加速内皮祖细胞的再内皮化”Circ Res. 93. 980-989 (20
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Fujiyama S, Amano K, Matsubara H.: "Matsubara H. Bone Marrow Monocyte-Lineage Cells Adhere on Injured Endothelium by MCP-1-Dependent Manner and Accelerate Reendothelialization as Endothelial Progenitor Cells"Circ Res. 93. 980-989 (2003)
Fujiyama S、Amano K、Matsubara H.:“Matsubara H. 骨髓单核细胞谱系细胞通过 MCP-1 依赖性方式粘附在受损的内皮上,并加速内皮祖细胞的再内皮化”Circ Res。
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共 23 条
    A molecular link between metabolic syndrome and energy metabolism in the heart
    • 批准号:
      23659423
    • 项目类别:
      Grant-in-Aid for Challenging Exploratory Research
    • 资助金额:
      $2.33万
    • 财政年份:
      2011
    • 负责人:
      MATSUBARA Hiroaki
    • 依托单位:
    Identification of priming factors that determine cardiac lineage of cardiac stem cells
    • 批准号:
      20249046
    • 项目类别:
      Grant-in-Aid for Scientific Research (A)
    • 资助金额:
      $31.12万
    • 财政年份:
      2008
    • 负责人:
      MATSUBARA Hiroaki
    • 依托单位:
    Cardiac Repair of Severe Heart Failure by Human Heart- or Skeletal Muscle-Derived Multipotent Stem Cells
    • 批准号:
      17209028
    • 项目类别:
      Grant-in-Aid for Scientific Research (A)
    • 资助金额:
      $31.7万
    • 财政年份:
      2005
    • 负责人:
      MATSUBARA Hiroaki
    • 依托单位:
    Angiogenic Cell Therapy by Bone Marrow-Derived Monocyte-lineage Stem Cells
    海外基金