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.

本研究旨在分析仓鼠-大鼠异种移植受体的微嵌合现象，并评价供体骨髓（DBM）扩增对异种移植物存活的影响。为了评价异种器官移植后MC的生物学意义，将肺和心脏受体均分为三组：I组未治疗; 2组接受短疗程的环磷酰胺FK 506; 3组接受长疗程的免疫抑制剂。在这些组中，MC的变化与肺移植物排斥反应的进展平行，而在心脏移植物中未检测到MC。第3组MC呈动态变化，在两个器官中均一度消失，然后又增加。MC的这种延迟发育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。异种肝/心移植后立即输注2.0X108 DBM。受体被分为4组：第1组未接受治疗;第2组输注DBM ;第3组接受（肝脏：FK 5 O 6/心脏：环磷酰胺和FK 506）;第4组输注DBM和短期免疫抑制剂。在两个器官中，第4组的MST显著长于第3组。肝移植术后第4组外周血MC状态持续时间明显长于第3组。在心脏组3中，仅在组4中观察到MC持续至第30天。总之，这些结果表明，伴随DBM增强促进MC，并显着延长异种移植物的存活，而无需长期免疫抑制治疗。但在这项研究中，MC是不持久的，不能实现持久的移植物接受。为了获得持久的异种MC，还需要进一步的研究。

项目成果

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。”

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。”

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。”

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）。