Xenogenic islet transplantation system based on tissue engineering

基于组织工程的异种胰岛移植系统

• 批准号: 10307027
• 负责人: INOUE Kazutomo
• 金额: $ 18.62万
• 依托单位: KYOTO UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (A).
• 财政年份: 1998
• 资助国家: 日本
• 起止时间: 1998 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-10307027/
• 关键词: islet translpantation; bioartificial pancreas; porcine islet; porcine endocrine cell; xenotransplantation; subcutaneous transplantation; neovascularization; controlled release of basic fibroblast growth factor; 異腫移植; 免疫隔離; ブタ膵内分泌細胞; ブタ膵島細胞; マイ

Transplantation of bioartificial pancreas is a fascinating method to cure diabetes. Recently, we have developed a 3-layer miaocapsule constituted of agarose-polystyrene sulfonic acid/polybrene/carboxymethyl cellulose. The 3-layer microcapsule could effectively prolong xenograft survival times without the use of immuno-suppressive drugs. In this project, we had been focusing mainly on the following studies ; to overcome the serious shortage of donor supply ; to establish a simpler and safer transplantation site than intraportal site ; to solve the problem of using microcapsule in islet transplantation.Novel Isolation methodsIn attempt to overcome the serious shortage of donor supply, we studied the novel method for isolation of adult pig islets. To divide the digestion procedure into two stage and to develop a new enzyme solution result in increasing the success rate of isolation of adult pig islets. Now, we are studying the method for isolation of porcinc endocrine cells to establish m … More ore stable method.Tissue engineering approach to construct the capillary network at subcutaneous site for bioartificial pancreasThe subcutaneous site has some advantages such as easy access with a minimally invasive procedure and a capability to retrieve the grafts easily but also has a disadvantages such as poor vascular distribution causing a loss of function of islet grafts in the early phase of the posttransplant period. In order to overcome this problem, we developed a basic fibroblast growth factor-releasing device to induce neovascularization at the subcutaneous site. Syngenic and xenogenic islet transplantation after inducing neovascularization result in significant decrease in nonfasting blood glucose of diabetic model animals.Development of 3-layer macrocapsuleIt is a disadvantage that microcapsule can not be retrieved from implantation site. We devecloped a 3-layer macrocapsule possessing the ability to protect host immunoattack and to be retrieved. Xenotransplantion using this device made it possible to control blood glucose level of diabetic animals. Less

生物人工胰腺移植是治疗糖尿病的一种有效方法。最近，我们开发了一种由琼脂糖-聚苯乙烯磺酸/聚苯乙烯/羧甲基纤维素组成的3层纳米胶囊。3层微胶囊可以在不使用免疫抑制药物的情况下有效延长异种移植物的存活时间。在这个项目中，我们主要集中在以下几个方面的研究；克服捐助者供应严重短缺的问题；建立比门静脉内移植更简单、更安全的移植部位；解决微胶囊在胰岛移植中的应用问题。为了解决猪胰岛供体严重短缺的问题，我们研究了一种分离成年猪胰岛的新方法。将消化过程分为两个阶段，并研制新的酶解液，提高了成年猪胰岛分离的成功率。目前，我们正在研究分离猪内分泌细胞的方法，以建立一种更稳定的方法。组织工程方法构建生物人工胰岛皮下毛细血管网络皮下毛细血管网络具有微创操作方便、易于提取移植物等优点，但也存在血管分布差导致胰岛移植物在移植后早期功能丧失的缺点。为了克服这个问题，我们开发了一种基本的成纤维细胞生长因子释放装置来诱导皮下部位的新生血管。同种和异种胰岛移植诱导新生血管后，糖尿病模型动物非空腹血糖显著降低。三层微胶囊的研制微胶囊不能从植入部位取出是一个缺点。我们开发了一种具有保护宿主免疫攻击和可回收能力的三层大胶囊。利用该装置进行异种移植，使控制糖尿病动物的血糖水平成为可能。少

项目成果

Nagata N: "Evaluation of Insulin Secretion of Isolated Rat Islets Cultured in Extracellular Matrix"Cell Transplant.. (印刷中).

Nagata N：“细胞外基质中培养的离体大鼠胰岛的胰岛素分泌评估”细胞移植..（出版中）。

Miyamoto M: "Development of cryopreservation procedure of freezer bag for pancreatic islets using newly developed cryoprotectant"Cell transplantation. (in press).

宫本 M：“使用新开发的冷冻保护剂开发胰岛冷冻袋冷冻保存程序”细胞移植。

Wanxing Cui: "The Tissue-engineering pancreatic Islets-Culturing The Rat Islets in The Chitosan Sponge"Cell transplantation. (in press). (2000)

崔万兴：“组织工程胰岛——在壳聚糖海绵中培养大鼠胰岛”细胞移植。

Miyamoto M.: "Effectt of Acidic Oxidative Potential Water on Microbial Contamination Harvesting Porcine Pancreas for Islet Xenotrasplantation"Transplant Proc. 30. 3431-3432 (1999)

宫本 M.：“酸性氧化电位水对用于胰岛异种移植的猪胰腺微生物污染的影响”移植过程。

K.Inoue: "Islet transplantation"J.Hepatobiliary Pancreatic Surgery. 7. 163-177 (2000)

K.Inoue：“胰岛移植”J.肝胆胰外科。