Experimental Research of Xeno Heart Transplantation

异种心脏移植的实验研究

• 批准号: 62480301
• 负责人: SADA Masaharu
• 金额: $ 3.97万
• 依托单位: National Cardiovascular Center, Research Institute
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (B)
• 财政年份: 1987
• 资助国家: 日本
• 起止时间: 1987 至 1989
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-62480301/
• 关键词: Xeno transplantation; Hyperacute resection; Histocomphtibility antigens; Mixed lymphocyte reaction; Xeno antibody; 主要組織適合性抗原系; モノクロ-ナルclass I抗体; 異種ドナ-選択; ジチオスレイト-ル(DTT); 補体依存性細胞障害試験; 非特異的IgM抗体; ヒト由来class I同種抗血清; 異種心臓移植; 霊長類組織適合性抗原系; 異種ドナー選択

1. Histopathological Changes on Macaque Hearts Perfused with Human Blood by Using Cardio-pulumonary Machine.(1) Case 1 : Coronary Perfusion by Using ABO Imcompatible Human Whole Blood(2) Case 2 : Coronary Perfusion by Using ABO Compatible Human Whole Blood(3) Case 3 : Coronary Perfusion by Using ABO Compatible and Plasma Removed Human BloodAt the macroscopy, case 1 and 2 were observed edema and diffuse bleeding within 15 minutes after coronary perfusion started. After 30 minutes, Macaque hearts resulted in ventricular fibrillation and arrested. Case 3 was well beating and there was no macroscopic changes during observation. At the histopathological examination of RV, LV and IVS, case 1 and 2 were observed severe interstitial bleeding, contraction band necrosis, mononuclear infiltration and intra-arterial thrombus. But patchy necrosis was observed all cases. It was suggested that these histopathological changes like a hyperacute rejection were due to xeno-antibodies in human plasma.2. A … More nalysis of cross-reactive Macaque histocompatibility antigens by using HLA alloantisera derived from human and monoclonal antibodies against HLA antigens.Four hundred and sixty three HLA-class I and 81 monoclonal antibodies against HLA-class I antigens, submitted to 10th International Histocompatibility Workshop, were typed by Macaque lymphocytes using complement dependent cytotoxicity test. In 136 of 463 alloantisera were reacted strongly because of xeno-antibodies. HLA antigens, across the barrier of species, defined mono-specific were HLA-A1, -A2, -B40 (w60, w61), -B5 (51, w52), -B27, -21, -Cw1 and Cw2. HLA Antigens defined multispecific were A10 (25, 26) -Aw19 (31, 32, w33), B5-B35-B15 (w62, w63), a part of B7-B27, a part of B7-B40 (w60, w61) and B12 (44, 45) -B21-B5. It was suggested the possibility that histocompatibility antigens, across the barrier of species, were defined by using common HLA antisera and were able to select the suitable donor for xeno-transplantation from the obtained matching grades. Less

1. 心肺机灌注人血对猕猴心脏组织病理学的影响。(1)病例1：用ABO不相容的人全血灌注冠状动脉(2)病例2：用ABO相容的人全血灌注冠状动脉(3)病例3：用ABO相容的去血浆的人血液灌注冠状动脉在冠脉灌注开始后15分钟内，病例1和病例2观察到水肿和弥漫性出血。30分钟后，猕猴的心脏出现心室颤动并停止跳动。病例3跳动良好，观察无宏观变化。左室、左室、左室组织病理学检查，病例1、2均可见严重间质出血、收缩带坏死、单核浸润及动脉内血栓形成。所有病例均可见斑片状坏死。我们认为这些组织病理变化如超急性排斥反应是由人血浆中的异种抗体引起的。利用人HLA异体抗血清和HLA抗原单克隆抗体，进一步分析猕猴组织相容性抗原的交叉反应性。在第10届国际组织相容性研讨会上，用补体依赖性细胞毒性试验，用猕猴淋巴细胞分型了463个hla I类抗体和81个针对hla I类抗原的单克隆抗体。463种异体抗血清中有136种因异种抗体而反应强烈。HLA抗原跨越物种屏障，定义为单特异性的HLA- a1， -A2, -B40 (w60, w61), -B5 (51, w52), -B27, -21， -Cw1和Cw2。定义为多特异性的HLA抗原有A10 (25,26) -Aw19 (31,32, w33), B5-B35-B15 (w62, w63)，部分B7-B27，部分B7-B40 （w60, w61）和B12 (44,45) -B21-B5。这表明组织相容性抗原可能跨越物种屏障，通过使用共同的HLA抗血清来定义，并能够从获得的匹配等级中选择合适的异种移植供体。少

项目成果

Hidemiki Sasaki: Transplanfation Procecdings. XIX. 1062-1064 (1987)

佐佐木秀树：移植论文集。

笹木秀幹: 日本移植学会誌.

佐佐木秀树：日本移植学会杂志。

笹木秀幹: 厚生省循環器病研究報告集. 1985. 280-281 (1985)

佐佐木秀树：卫生福利部心血管疾病研究报告集 1985。280-281 (1985)

佐田正晴: 日本移植学会誌.

Masaharu Sada：日本移植学会杂志。

TSUNEHIKO NISHIMURA: CARDIOVASCULAR RESEARCH. XXII-2. 108-112 (1988)

西村常彦：心血管研究。