Development of Hybrid Artificial Liver with Isolated Hepatocytes in Extracorporeal Circulation

体外循环分离肝细胞混合人工肝的研制

基本信息

  • 批准号:
    06454381
  • 负责人:
  • 金额:
    $ 4.16万
  • 依托单位:
  • 依托单位国家:
    日本
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
  • 财政年份:
    1994
  • 资助国家:
    日本
  • 起止时间:
    1994 至 1995
  • 项目状态:
    已结题

项目摘要

In an attempt to develop a hybrid artificial liver (HAL) using isolated hepatocytes, we prepared hollow fiber modules with hepatocytes entrapped in collagen gel and evaluated the HAL devices in hepatic failure models. And we studied the hypothermic preservation (4゚C) of hepatocytes entrapped in collagen gel, for the purpose of storage of the HAL devices.In rats experiments, the modules contained 4*10^7 rat hepatocytes were evaluated by extracorporeal hemoperfusion. In ischemic hepatic failure models, the device revealed ammonia removal and gluconeogenesis. Drug (galactosamin) induced acute hepatic failure rats showed the improvement of total bile acid and GOT in extracorporeal hemoperfusion. The devices demonstrated the supporting failing functions on host livers.In rabbits experiments, the modules contained 3.5*10^8 rabbit hepatocytes were evaluated. Perfusion culture was performed and demonstrated good maintenance of differentiated liver functions of albumin secretion, ureogenesis and ammonia removal at Day 0. Perfusion solution showed appearance of a protein with same molecular weight as in rabbit serum. The devices were evaluated as a HAL by extracorporeal hemoperfusion using one or two modules in anhepatic rabbits. In the single HAL groups, blood pressure were significantly maintained. Increase in serum ammonia was inhibited and survival time were significantly prolonged. In the double HAL groups, lactic acid, prothrombin time and Fisher ratio were improved significantly.These studies provided the evidence that our HAL system included detoxicating, synthetic and metabolic functions, and it may be clinically useful in the future.We studied the preservation of hepatocytes entrapped in collagen gel in 4゚C University of Wisconsin solution. Preserved hepatocytes in our system showed round-shaped morphology in phase-difference and scanning electron microscopy. They maintained adequate functional capability even after 14 days of preservation.
在尝试开发一个混合型人工肝(HAL)使用分离的肝细胞,我们制备了中空纤维模块与肝细胞包埋在胶原凝胶和评估的HAL装置在肝衰竭模型。在大鼠实验中,通过体外血液灌流对含有4*10^7个大鼠肝细胞的模块进行了评价。在缺血性肝衰竭模型中,该装置显示氨清除和再生。药物(氨基半乳糖)诱导的急性肝功能衰竭大鼠体外血液灌流可改善总胆汁酸和GOT。在兔实验中,对包含3.5*10^8个兔肝细胞的模块进行了评估。进行了灌注培养,并在第0天证明了白蛋白分泌、尿素生成和氨清除的分化肝功能的良好维持。灌流液中出现与兔血清中分子量相同的蛋白质。通过在无肝兔体内使用一个或两个模块进行体外血液灌流,将这些设备评估为HAL。在单一HAL组中,血压显著维持。血氨升高受到抑制,存活时间显著延长。结果表明,双HAL组的乳酸、凝血酶原时间和Fisher比值均明显改善,说明我们的HAL系统具有解毒、合成和代谢的功能,有可能应用于临床。在相差显微镜和扫描电镜下,我们系统中保存的肝细胞呈圆形形态。即使在保存14天后,它们仍保持足够的功能能力。

项目成果

期刊论文数量(40)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
小玉,正智 他: "コラーゲンゲル内ラット肝細胞長期培養法" 応用細胞生物学研究. Vol.11. 23-34 (1994)
Kodama, Masato 等:“胶原凝胶中大鼠肝细胞的长期培养方法”应用细胞生物学研究卷 11. 23-34 (1994)。
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    0
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  • 通讯作者:
小玉正智 他: "Hepatocytes Entrapped in Collagen-gel Following 14 Days of Storage at 4℃ (Preservation of Hybrid Artificial Liver)" Artificial Organs. Vol. 21. 99-106 (1997)
Masatomo Kodama 等人:“4℃ 保存 14 天后被胶原蛋白捕获的肝细胞(混合人工肝脏的保存)”Artificial Organs,第 21 卷 99-106(1997 年)。
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    0
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MASASHI KODAMA et.al.: "HYBRID ARTIFICIAL LIVER USING HEPATOCYTES ENTRAPPED WITH COLLAEN GEL IN A HOLLOW FIBER DEVICE" Japanese Journal of Apheresis. Vol.16 (1). 215-216 (1997)
MASASHI KODAMA 等人:“在中空纤维装置中使用胶原凝胶捕获的肝细胞进行混合人工肝”,《日本血浆分离术杂志》。
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    0
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小玉正智 他: "High Cell-density Culture System of Hepatocyte Entrapped in Three Dimensinal Hollow Fiber Module with Collagen Gel." Artificial Organs. Vol. 19. 191-193 (1995)
Masatomo Kodama 等人:“用胶原凝胶包裹在三维空心纤维模块中的高细胞密度培养系统”,第 19 卷,191-193 (1995)。
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  • 影响因子:
    0
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  • 通讯作者:
小玉正智 他: "Hybrid Artiticial Liver Using Hepatocytes Entrapped with Collagen Gel in a Hollow Fiber Device" Japanese Journal of Apheresis. Vol. 16. 215-216 (1997)
Masatomo Kodama 等人:“使用中空纤维装置中夹带胶原凝胶的肝细胞进行混合人工肝”,《日本血液成分分析杂志》,第 16 卷,215-216(1997 年)。
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KODAMA Masashi其他文献

KODAMA Masashi的其他文献

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{{ truncateString('KODAMA Masashi', 18)}}的其他基金

Studies on the Inhibitory Effect of Blood Transfusion Against Anti-Tumor Immunity
输血抗肿瘤免疫抑制作用的研究
  • 批准号:
    01480312
  • 财政年份:
    1989
  • 资助金额:
    $ 4.16万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
evaluation and invention of endotoxin detoxifying material for clinical application
内毒素解毒材料的临床应用评价及发明
  • 批准号:
    62870051
  • 财政年份:
    1987
  • 资助金额:
    $ 4.16万
  • 项目类别:
    Grant-in-Aid for Developmental Scientific Research
Study on the mechanical analysis of septic shock and its theraputic strategy
感染性休克的力学分析及治疗策略研究
  • 批准号:
    62480271
  • 财政年份:
    1987
  • 资助金额:
    $ 4.16万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)
The study for new therapy of endotoxin shock
内毒素休克新疗法的研究
  • 批准号:
    60480291
  • 财政年份:
    1985
  • 资助金额:
    $ 4.16万
  • 项目类别:
    Grant-in-Aid for General Scientific Research (B)

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  • 批准号:
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Development of a hybrid artificial liver with hepatocytes derived embryonic stem cell for chronic liver failure patients
为慢性肝衰竭患者开发具有肝细胞来源的胚胎干细胞的混合人工肝
  • 批准号:
    16206079
  • 财政年份:
    2004
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  • 财政年份:
    2002
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Construction of Hybrid Artificial Liver with Immortalized Human Hepatocytes
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  • 批准号:
    12671175
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    1997
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Construction of Hybrid Artificial Liver with Immortalized Human Hepatocytes
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  • 批准号:
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Development of an hybrid artificial liver for human medical use equipped with the newest regulation system for control of culture environment of hepatocytes
开发配备最新肝细胞培养环境控制系统的医用混合人工肝
  • 批准号:
    06555248
  • 财政年份:
    1994
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Construction of Hybrid Artificial Liver with Immortalized Human Hepatocytes.
永生化人肝细胞混合人工肝的构建。
  • 批准号:
    05807109
  • 财政年份:
    1993
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原代培养肝细胞中肝脏特异性基因表达的研究用于建立混合型人工肝
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HYBRID ARTIFICIAL LIVER USING IMMOBILIZED HEPATOCYTES
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