Induction of immunotolerance using non-myeloablating stem cell transtplantation in swine model of small intestinal transplantation

非清髓性干细胞移植在猪小肠移植模型中诱导免疫耐受

• 批准号: 17390352
• 负责人: TAGUCHI Tomoaki
• 金额: $ 10.64万
• 依托单位: Kyushu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (B)
• 财政年份: 2005
• 资助国家: 日本
• 起止时间: 2005 至 2007
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-17390352/
• 关键词: small intestinal transplantation; non-myeloablating stem cell transplantation; chimerism; immunotolerance; MHC; large animal; miniature swine; living-related transplantation

Survival rate after Small intestinal transplantation has been improved gradually in recent 10 years. However, incidence of acute as well as chronic rejection is still high, and late graft loss is sometimes happen. In order to overcome immunological obstacles, induction of tolerance is called for.Non-myeloablating stem cell transplantation has been introduced as treatment tool for leukemia. In living-related organ transplantation, donor specific tolerance can be induced by this method. After tolerance induction by stem cell transplantation, small intestinal graft from the same donor can be accepted without immunosuppression. We have starting to establish this method using mini-swine model of small intestinal transplantation.In the first year, operion technique of small intestinal transplantation, using miniature swine was established. Ileal graft was harvested with pedicle. Cutting site of each superior mesenteric vessel was radix of celiac trunks and portal vein. Then graft was anastosed to Aorta and graft vein was anastomosed to IVC by end-to-side fashion.In the second year, non-myeloablating stem cell transplantation was started. Bone marrow cells were harvested from iliac bone. However the number of cells were not enough for tstem cell transplantation. Then we started irrigation of bone marrow, using two needle. After that the number of cells were increased. The numbers were identified by CD34 immunostaining.In the third year, miniature swine, SLA established syngenic chrone, cannot be supplied by animal farm. Especially, combination of SLA 1 mismatch is impossible now. We have proposed the protochol of chemotherapy which can establish the non-myelloablating protochol.

近10年来，小肠移植术后的生存率逐渐提高。然而，急性和慢性排斥反应的发生率仍然很高，有时发生晚期移植物丢失。为了克服免疫学障碍，需要诱导耐受，非骨髓清除性干细胞移植已被引入白血病的治疗工具。在活体器官移植中，可以通过这种方法诱导供体特异性耐受。经干细胞移植诱导免疫耐受后，同一供者小肠移植物可在无免疫抑制的情况下被接受。本实验室已开始建立小型猪小肠移植模型，并在第一年建立了小型猪小肠移植手术技术。带蒂取回肠移植物。各上级肠系膜血管的切断部位为腹腔干根部和门静脉。移植物与主动脉端侧吻合，移植静脉与下腔静脉端侧吻合，第2年开始非骨髓清除干细胞移植。从髂骨收获骨髓细胞。然而，细胞的数量不足以进行干细胞移植。然后我们开始用两根针冲洗骨髓。之后，细胞数量增加。第三年，小型猪（SLA）建立了同系世代，猪场不能供应。特别是SLA 1不匹配的组合现在是不可能的。我们提出了化疗方案，建立了非髓性方案。

项目成果

The evidence of maternal microchimerism in biliary atresia using fluorescent in situ hybridization

• DOI: 10.1016/j.jpedsurg.2007.08.039
• 发表时间: 2007-12-01
• 期刊: JOURNAL OF PEDIATRIC SURGERY
• 影响因子: 2.4
• 作者: Hayashida, Makoto;Nishimoto, Yuko;Taguchi, Tomoaki
• 通讯作者: Taguchi, Tomoaki

Clinical features of selenium deficiency in infants receiving long-term nutritional support

• DOI: 10.1016/j.nut.2007.08.001
• 发表时间: 2007-11-01
• 期刊: NUTRITION
• 影响因子: 4.4
• 作者: Masumoto, Kouji;Nagata, Kouji;Taguchi, Tomoaki
• 通讯作者: Taguchi, Tomoaki

Hirschsprung's disease in Japan: analysis of 3852 patients based on a nationwide survey in 30 years

• DOI: 10.1016/j.jpedsurg.2004.09.052
• 发表时间: 2005-01-01
• 期刊: JOURNAL OF PEDIATRIC SURGERY
• 影响因子: 2.4
• 作者: Suita, S;Taguchi, T;Nakatsuji, T
• 通讯作者: Nakatsuji, T

Successful prolonged rituximab treatment for post-transplant lymphoproliferative disorder following living donor liver transplantation in a child

成功延长利妥昔单抗治疗儿童活体肝移植后移植后淋巴细胞增殖性疾病的效果

• 发表时间: 2007
• 期刊: Pediatr Transplant 11
• 作者: Hayashida M;Ogita K;Matsuura T;Takahashi Y;Nishimoto Y;Ohga S;Hara T;Soejima Y;Taketomi A;Maehara Y;Kohashi K;Tsuneyoshi M;Taguchi T
• 通讯作者: Taguchi T

Safe techniques for inserting the hickman catheter in pediatric patients.

在儿科患者中插入希克曼导管的安全技术。

• 发表时间: 2006
• 期刊: Pediatr Hematol Oncol. 23(7)
• 作者: Masumoto K;Uesugi T;Nagata K;Takada N;Taguchi S;Ogita K;Yamanouchi T;Taguchi T;Suita S
• 通讯作者: Suita S