異種心移植における胎児期ドナー特異的免疫寛容の誘導

异种心脏移植中胎儿供体特异性免疫耐受的诱导

• 批准号: 09770911
• 负责人: 田中 佐登司
• 金额: $ 1.22万
• 依托单位: Tokyo Women's Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Encouragement of Young Scientists (A)
• 财政年份: 1997
• 资助国家: 日本
• 起止时间: 1997 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-09770911/
• 关键词: 異種心移植; キメラ; 免疫寛容; 胎児

【目的】現在心臓移植を取り巻く問題として慢性的な臓器不足,各種免疫抑制剤の投与により発生する重症感染症等が存在する.免疫抑制剤を一切使用せずドナー特異的な免疫寛容状態を異種間移植で誘導する事が移植医療の理想である.ラット,ハムスター間異種心移植モデルを用い,胎児期にドナー特異的な免疫寛容を誘導する事を目的とした.【方法】 ドナーにゴールデンハムスター,レシピエントにのLewisラットを用い全身麻酔下Ono-Lindsey法に従い腹腔内異所性心移植を施行した(n=8).妊娠9,16日目のLewisラットを同様に麻酔し開腹.ドナーより採取した骨髄細胞を子宮内へ注入し閉腹妊娠を継続させ出産.胎児出生後これをレシピエントとし,同様に腹腔内異所性心移植を施行(妊娠9日群:n=8,妊娠16日群:n=5).同時にレシピエントの染色体分析を施行した.【結果】移植心生着期間はコントロール群2.5±0.5,妊娠9日群7.4±4.1,妊娠16日群2.8±0.8日であった.コントロール群と妊娠9日群間では統計学的有意差を認めた(p<0.008)が,妊娠16日群では認められなかった.妊娠9日群と妊娠16日群のレシピエントラットの染色体分析を施行し妊娠9日群ではLewisラットの染色体以外にゴールデンハムスターの染色体を認めた.【結語】1.ラット,ハムスター間異種心移植モデルを用い,ドナー骨髄細胞のレシピエント妊娠前期投与群では移植心生着期間の有意な延長が認められたが,妊娠後期投与群では延長は認められなかった.2.ドナー骨髄細胞をレシピエントの子宮内に直接投与する事によりキメリズムが示唆された.3.ドナー特異的免疫寛容を誘導する事により異種間心臓移植の可能性が示唆された.

[objective] at present, there is a shortage of chronic immunosuppressive devices in cardiac transplantation, and there are some problems such as severe infections in patients with severe infections. Immunosuppression tests all transplants that use specific immune status to guide transplant physicians and doctors. The purpose of this study was to determine the immune capacity of fetal heart transplant. [methods] to treat heart transplantation with general anesthesia, Ono-Lindsey and abdominal cavity transplantation were performed under general anesthesia (Ono-Lindsey method). On the 9th and 16th of pregnancy, Lewis pregnant women underwent abdominal surgery with anaesthesia. The bone was injected into the uterus of abdominal pregnancy. After birth, the fetal heart transplantation was carried out in the same way as in the abdominal cavity (9 days of pregnancy: nude 8, 16 days of pregnancy: nude 5). At the same time, the chromosome analysis was carried out by chromosome analysis. [results] during the period of heart transplantation, the pregnancy population was 2.5 ±0.5, the 9-day group was 7.4 ±4.1, and the 16-day group was 2.8 ±0.8 days old. The intentional error of intergroup statistics of pregnancy was 0.008 on the 9th day of pregnancy, and on the 16th day of pregnancy. On the 9th day of pregnancy, the chromosome analysis was performed in the group of pregnant women on the 16th day of pregnancy. [results] 1. The chromosome analysis was performed in the group of 9 days of pregnancy. [results] 1. In the first trimester of pregnancy, there was an intention to prolong the pregnancy rate during the first trimester of pregnancy, and in the second trimester of pregnancy. 2. I don't know what to do. I don't know. I don't know. I don't know. The possibility of heart transplant is instigated by the possibility of special immune tolerance.

项目成果

Satoshi A.Tanaka: "Induction of Donor-Specific Tolerance to Cardiac Xenogiatos in Utero." The Journal of Heart and Lung Transplantation. 17. 888-891 (1998)

Satoshi A.Tanaka：“诱导子宫内心脏异种的供体特异性耐受。”

田中佐登司, 他: "短絡疾患に合併した感染性心内膜炎の特徴とその外科治療" 日本胸部外科学会雑誌. 42(7). 1032-1037 (1994)

Satoshi Tanaka 等：“分流性疾病并发感染性心内膜炎的特点及其手术治疗”日本胸外科杂志 42(7) (1994)。