Studies on Regenerative Medicine for Diabetes Mellitus by Cell Biology

糖尿病患者的数量在全球范围内明显增加，严重并发症如肾病和视网膜病变的发生率也在增加。胰腺和胰岛移植可以有效地治疗严重的糖尿病，但不可避免地存在供体短缺和免疫抑制相关的问题。生物人工胰腺是一种治疗方式，通过这种治疗方式，异体甚至异种胰岛可以在没有免疫抑制的情况下使用。在几种生物人工胰腺中，胰岛大囊化是最具临床应用前景的方法：我们提出了一种用聚乙烯醇(PVA)水凝胶大囊化胰岛的新方法，并对其工艺和实用性进行了研究。我们还研究了纤维蛋白和其他药物在可以移植大囊化胰岛(MEI)的皮下部位新生血管的新方法。我们进一步研究了胰岛细胞与间充质干细胞之间的细胞融合，为糖尿病治疗寻找新的细胞来源。将含有大鼠胰岛的片状PVA溶液冷冻解冻后制成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灾难，提高了存活率，保护了肾脏免受糖尿病肾功能障碍的影响。将PVA-Mei移植到同基因和同基因情况下的糖尿病大鼠体内。移植后高血糖持续数周下降，两组间差异无显着性。这些结果和其他发现一起表明，大胶囊有效地保护胰岛免受同种和异种免疫调节，需要进一步改进处理和其他方法来延长移植的效果。

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.