Tolerance induction by biological modulation in allogeneic and xenogeneic

同种异体和异种生物调节的耐受诱导

• 批准号: 08457302
• 负责人: ASAHARA Toshimasa
• 金额: $ 4.99万
• 依托单位: HIROSHIMA UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 1996
• 资助国家: 日本
• 起止时间: 1996 至 1998
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-08457302/
• 关键词: xenogeneic transplantation; biological modulation; microchimerism; bone marrow augmentation; 異種臓器移植; hamster-to-rat肝移植; microchimerism; ドナー放射線照射; recipient骨髄細胞門脈投与

This study was designed to analyze the microcimerism (MC) in the hamster-to-rat xenografted recipients, and to evaluate the effect of donor bone marrow (DBM) augmentation on xenograft survival. We established the method using PCR for detection of MC in hamster-to-rat combination To assess the biological relevance of MC after organ xenotransplantation, both lung and heart recipients were divided into three groups : group I were untreated ; group 2 received short course of cyclophosphamide FK506 ; and group 3 were treated with a long course of immunosuppressants. In these groups, MC changed in parallel with the progression of rejection in lung grafts, whereas it was not detected in heart grafts. In group 3, MC changed dynamically ; once disappeared and then it increased in both organs. This delayed development of MC suggests the existence of donor passenger leukocytes in the recipients that had the character of the hematopoietic stem cells. Hamster DBM (2.OX108) were infused immediately after liver/heart xenotransplanration. Recipients were divided into four groups : group 1 were untreated ; group 2 were infused with DBM ; group 3 received a (liver : FK5O6/heart : cyclophosphamide and FK506) ; and group 4 were infused with DBM and short course of immunosuppressants. In both organs MST for group 4 were significantly longer than that for group 3. The duration of the MC state in the peripheral blood was clearly longer in group 4 thanin group 3 after liver transplantation. In heart group 3, MC was observed in only group 4 continuously until day 30. In conclusion, these findings suggest that concomitant DBM augmentation promoted MC in and markedly prolonged the xenograft survival without long standing immunosuppressive therapy. But in this study, MC was not persistent, and long-lasting graft acceptance could not be achieved. In order to make persistent xenogeneic MC, further studies are required.

这项研究旨在分析仓鼠异种移植受体中的微核酸（MC），并评估供体骨髓（DBM）增强对异种移植生存的影响。我们使用PCR建立了该方法在仓鼠到鼠标组合中检测MC，以评估器官异种移植后MC的生物学相关性，将肺和心脏的受体分为三组：第一组未经治疗；第2组获得了短期的环磷酰胺FK506；和第3组用长期的免疫抑制剂治疗。在这些组中，MC与肺移植物中排斥反应的进展并行变化，而在心脏移植中未检测到。在第3组中，MC动态变化；一旦消失了，然后在两个器官中都增加了。 MC的这种延迟发展表明，在具有造血干细胞特征的受体中存在供体乘客白细胞。肝脏/心脏异种转导后立即注入仓鼠DBM（2.OX108）。接受者分为四组：第1组未经治疗；第2组注入DBM；第3组接受了（肝脏：FK5O6/心脏：环磷酰胺和FK506）；和第4组注入了DBM和短暂的免疫抑制剂。在这两个器官中，第4组的MST均明显长于第3组。在肝移植后第4组中，外周血中MC状态的持续时间显然更长。在第3个心脏组中，仅在第4组中观察到MC，直到第30天。总之，这些发现表明，伴随的DBM增强促进了MC，并明显延长了异种移植物的生存，而没有长期存在的免疫抑制治疗。但是在这项研究中，MC并不持久，无法实现持久的移植物接受。为了进行持续的异构MC，需要进一步的研究。

项目成果

Miyata Y,Ohdan H,Noriyuki T,Shintaku S,Shibata S,Yamamoto H,Fudaba Y,Tashiro H,X.H.Fan, Yoshioka S,Asahara T,Fukuda Y,Dohi K: "Development of xenogeneic microchimerism correlated with graft outcome in hamster-to-rat heart xenotransplantation." Transplant

Miyata Y、Ohdan H、Noriyuki T、Shintaku S、Shibata S、Yamamoto H、Fudaba Y、Tashiro H、X.H.Fan、Yoshioka S、Asahara T、Fukuda Y、Dohi K：“异种微嵌合体的发展与仓鼠移植结果相关

Ohdan H,: "Prolongation of hamster-to-rat liver xenograft survival by donor bone marrow augmentation." Transplant Proc. (in press). Tashiro H, (1997)

Ohdan H，：“通过供体骨髓增强延长仓鼠至大鼠肝脏异种移植物的存活率。”

Miyata Y: "Analysis of xenogeneic microchimerism in hamster-to-rat lung xenotransplantation." Transplant Proc. 29. 3505-3507 (1997)

Miyata Y：“仓鼠至大鼠肺异种移植中异种微嵌合的分析。”

Induction of donor specilic hyporeactivity in augmented microchimerism in liver grafting rat followed by donor specilic bone marrow transplantation.: "Transplant Proc" (in press). 1997.

在肝移植大鼠中诱导供体特异性低反应性增强微嵌合，然后进行供体特异性骨髓移植。：“移植过程”（正在印刷中）。

Tashito H,: "Asessment of Microchimerism in rat liver transplarntation by polymerase chain reaction." Hepatology. 23 (4). 825-834 (1996)

Tashito H，：“通过聚合酶链反应评估大鼠肝移植中的微嵌合。”