Living donor islet transplantation for the treatment of sever diabetes

活体胰岛移植治疗严重糖尿病

基本信息

批准号：
15390376
负责人：
MATSUMOTO Shinichi
金额：
$ 9.47万
依托单位：
KYOTO UNIVERSITY
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (B)
财政年份：
2003
资助国家：
日本
起止时间：
2003 至 2004
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15390376/
关键词：
Living donor islet transplantation Living donor Islet isolation method Non-heart-beating donor GMP facility Type 1 diabetes 生体膵島移埴膵島分離技術インスリン依存状態糖尿病膵島移植 GMP ISO9001 ブタ膵島膵管保護二層法膵保存

项目摘要

We performed the world first successful living donor islet transplantation (Matsumoto S, et al. Lancet 2005). Since this is the first time to be shown that diabetes can be cured by living donor cell transplantation, many newspapers, magazines and media mentioned about this historical success. NATURE magazine put the title 'Mother-to-daughter transplant reverses diabetes' for this news and LANCET magazine published this research on early online publication.The recipient suffered insulin dependent diabetes mellitus since 15 years old. She received living donor islet transplantation after 12 yeas after her onset and she is now free from insulin therapy. Her oral glucose tolerance test was normal pattern. The donor was 57 years old female and the mother of the recipient. She discharged within 3 weeks and she returned her job within one month. She is also normal glucose metabolism and her oral glucose tolerance test was also normal pattern.For this historical success, many researches had ac … More complished. At first, new reliable islet isolation method 'Kyoto islet isolation method' was established after comprehensive large animal research (Matsumoto S et al. Transplantation in press). With the Kyoto islet isolation method, we were able to isolate and transplant islets into diabetic patients using non-heart-beating donor for the first time in Japan (Matsumoto S et al. Transplantation in press). The patient became insulin independent for the first time in Japan and this is world second case that diabetic patient was cured by islet transplantation using non-heart-beating donor. After this success we performed 14 islet isolations using non-heart-beating-donors and transplanted 12 cases. The success rate of islet isolation was 86% and this is truly remarkable. In the US, they usually are able to transplant less than 50% even using high quality brain-dead-donors. Since it is very important to establish reliable islet isolation method for living donor islet transplantation, Kyoto islet isolation method is critical invention.We also submitted a patent application for Kyoto islet isolation method. The manuscript about Kyoto islet isolation method was accepted within one month after submission by TRANSPLANTATION. We presented this method at 10^<th> international pancreas and islet transplantation association congress in Geneva. After this presentation, many islet isolation and transplantation offered collaboration to use Kyoto islet isolation method in their institute. We are sure that Kyoto islet isolation method is also useful for brain-dead donor islet isolation and transplantation, and this method will bring the islet transplantation from experimental phase to real clinical treatment phase.Another important finding was that tail part of the human pancreas should be suitable for islet isolation (Matsumoto S et al. Transplantation 2004). This experiment was collaboration with Human Islet Transplant in Seattle program. This study demonstrated that tail section of pancreas could provide enough islet yields for successful islet transplantation.In addition, we developed new system for drug delivery and demonstrated effective immuno suppressive drugs with lesser side effects in islet transplantation model for future clinical application (H.Noguch, S.Matsumoto et al. Nature Medicine 2004).In summarize, we were established Kyoto islet isolation method for reliable islet transplantation. Using this method, we were able to perform the world first successful living donor islet transplantation. Less

我们进行了世界上首次成功的活体胰岛移植（Matsumoto S, et al. Lancet 2005），由于这是第一次证明糖尿病可以通过活体供体细胞移植来治愈，因此许多报纸、杂志和媒体都提到了这一点。历史性的成功。《自然》杂志将这一消息命名为“母女移植逆转糖尿病”，《柳叶刀》杂志在早期在线出版物上发表了这项研究。接受者从 15 岁起就患有胰岛素依赖型糖尿病。她在发病 12 年后接受了活体供体胰岛移植，现在已不再接受胰岛素治疗。供体是 57 岁的女性，受体的母亲在 3 周内出院。她在一个月内回到了工作岗位，她的葡萄糖代谢也正常，她的口服葡萄糖耐量测试也正常。为了这一历史性的成功，许多研究首先完成了新的可靠的胰岛分离方法“京都胰岛分离”。 “方法”是在综合大型动物研究后建立的（Matsumoto S等人的移植正在出版）通过京都胰岛分离方法，我们首次能够使用无心跳供体分离胰岛并将其移植到糖尿病患者体内。日本（Matsumoto S 等移植正在出版）日本首次实现胰岛素依赖，这是继无心跳供体的胰岛移植后世界第二例糖尿病患者。我们使用非心跳供体进行了 14 例胰岛分离，并移植了 12 例。胰岛分离的成功率为 86%，这在美国是非常了不起的，即使使用非心跳供体，他们通常也能移植不到 50%。建立可靠的脑死亡供体胰岛分离方法对于活体胰岛移植非常重要，京都胰岛分离方法是关键发明。我们还提交了京都胰岛分离的专利申请。关于京都胰岛分离方法的稿件在TRANSPLANTATION提交后一个月内被接受，我们在日内瓦举行的第10届国际胰腺和胰岛移植协会大会上发表了该方法，之后许多胰岛分离和移植提出了合作。在他们的研究所使用京都胰岛分离方法，我们确信京都胰岛分离方法对于脑死亡供体胰岛分离和移植也有用，并且该方法将带来实验性的胰岛移植。另一个重要的发现是人类胰腺的尾部应该适合胰岛分离（Matsumoto S et al. Transplantation 2004），该实验是与西雅图人类胰岛移植计划合作进行的。胰腺尾部切片可以为成功的胰岛移植提供足够的胰岛产量。此外，我们开发了新的药物输送系统，并在胰岛移植模型中证明了有效且副作用较小的免疫抑制药物，以供将来的临床应用(H.Noguch, S.Matsumoto 等人，Nature Medicine 2004)。总之，我们建立了可靠的胰岛移植京都胰岛分离方法，利用该方法，我们能够成功地进行世界上首次活体胰岛移植。