Studies on Regenerative Medicine for Diabetes Mellitus by Cell Biology

随着糖尿病肾病、视网膜病变等严重并发症的发生率的增加，糖尿病患者的数量在世界范围内明显增加。可以有效治疗严重糖尿病的胰腺和胰岛移植仍然存在供体短缺和免疫抑制相关问题。生物人工胰腺是一种治疗模式，通过它可以使用同种异体甚至异种异体胰岛而无需免疫抑制。在各种生物人工胰腺中，胰岛微囊化是最有应用前景的一种装置：用途：我们采用聚乙烯醇（PVA）水凝胶微囊化胰岛，并对微囊化胰岛的工艺进行了改进。我们还研究了纤维蛋白和其他药物在皮下部位的新血管形成的新方法，其中巨囊胰岛（MEI）可以移植。为进一步研究胰岛细胞与间充质干细胞的融合，为糖尿病的治疗寻找新的细胞来源，我们将含胰岛细胞的片状聚乙烯醇（PVA）溶液冻融，制备成PVA-MEI。将该装置移植到糖尿病小鼠或大鼠体内，PVA-MEI移植显著改善了糖尿病小鼠的高血糖和代谢损害，提高了存活率，并保护了肾脏免受糖尿病肾功能损害。PVA-MEI移植到糖尿病大鼠在同基因和异基因的情况下。移植后数周血糖下降，两组间无显著差异。这些结果与其他发现一起表明，巨囊包封有效地保护胰岛免受同种异体和异种免疫排斥，并且需要进一步改进处理和其他方法以延长移植的功效。

The number of patients suffering from diabetes mellitus is apparently increasing all aver the world with the growing incidence of severe complications such as nephropathy and retinopathy. Pancreas and islet transplantation by which severe diabetes can be effectively treated retain inevitable problems of donor shortage and immuno-suppression-related issues. Bio-artificial pancreas is a therapeutic modality by which allo- and even xeno-geneic islets can be used without immuno-suppression. In several kinds of bio-artificial pancreas, macro-encapsulation of the islets is the most promising device for clinical use : We developed a novel method of islet macro-encapsulation with poly vinyl alcohol (PVA) hydro-gel and studied several improvements of procession and its usefulness. We also studied fibrin and other agents in novel methods of neo-vascularization at the subcutaneous site where macro-encapsulated islets (MEI) can be transplanted. We further studied cell fusion between islet cells and mesenchymal stem cells to search new cell source for diabetes therapy.PVA-MEI was processed y freezing and thawing the sheet-shape-molded PVA solution containing rat islets. The device was transplanted to diabetic mice or rats.Transplantation of PVA-MEI significantly improved hyperglycemia and metabolic disaster of diabetic mice with better survival rate and protected kidney from diabetic renal dysfunction. PVA-MEI was transplanted to diabetic rats in iso- and allo-geneic situations. The transplantation decreased the hyperglycemia for several weeks without any remarkable difference between the situations. These results, together with other findings, indicate that macro-encapsulation effectively protect islets from allo- and xeno-geneic immune regection and that further improvement in processing and other methods are needed to elongate the efficacy of the transplantation.