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Studies on regenerative medicine for severe diabetes mellitus by stem cell biology

干细胞生物学对重症糖尿病再生医学的研究

基本信息

批准号：
16390360
负责人：
SUMI Shoichiro
金额：
$ 7.74万
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：
2004
资助国家：
日本
起止时间：
2004 至 2005
项目状态：
已结题

项目摘要

A new method of making bio-artificial pancreas (BAP), macro-encapsulation of islets in PET (polyethyren tetraphutarate) mesh-reinforced PVA (polyvinyl alcohol) gel by freezing and thawing, was developed. This BAP was found to keep islets viable and functional in comparison to normal free islets in vitro. Transplantation of this BAP ameliorated hyperglycemia and improved renal dysfunction and survival in mouse model of insulin-dependent diabetes mellitus. In studying subcutaneous transplantation of BAP, collagen-coated PVA bag, when applied with sustained release micro-sphere of basic FGF (fibroblast growth factor), was found to induce more angiogenesis and improved viability of included islets in comparison to non-coated PVA bag. Islet preservation studies revealed that apoptosis, a major mechanism of islet cell loss in islet transplantation tended to develop early after islet isolation and rapidly progressed during normal culture conditions. On the other hand, cold preservation in University Wisconsin solution was found to inhibit apoptosis. Pancreas regeneration studies in rats suggested that certain factors perhaps including hyperglycemia was activated by major pancreatectomy and maintained regenerative state of the remnant pancreas, since the weight of the remnant-equivalent pancreas was increased only temporally and returned to its normal weight if pancreatic duct corresponding to removed lobes in major pancreatectomy was ligated and left in the place.In stem cell studies, neuron-like cells obtained in the differentiation studies of mouse embryonic stem cells were found to improve the symptoms of Parkinson's disease in model rats. Differentiation form bone marrow-derived cells and epithelial cells of pancreatic duct to islet cells and electrical cell fusion of bone marrow cells and islet cells were also studied and interesting knowledge toward future studies was accumulated.

提出了一种新的制备生物人工胰腺（BAP）的方法，即将胰岛包埋在PET（聚乙烯四氟酸酯）网状增强聚乙烯醇（PVA）凝胶中，采用冷冻和解冻的方法制备生物人工胰腺。与正常的游离胰岛相比，这种BAP在体外可保持胰岛的活力和功能。移植该BAP可改善胰岛素依赖型糖尿病小鼠模型的高血糖，改善肾功能和生存。在BAP皮下移植研究中，胶原包被的PVA包被与碱性FGF（成纤维细胞生长因子）缓释微球一起应用时，发现与未包被的PVA包被相比，可诱导更多的血管生成并提高所含胰岛的活力。胰岛保存研究表明，细胞凋亡是胰岛移植中胰岛细胞损失的主要机制，在胰岛分离后早期发生，在正常培养条件下迅速发展。另一方面，威斯康辛大学溶液冷保存可抑制细胞凋亡。大鼠胰腺再生研究表明，胰大切除术激活了某些可能包括高血糖在内的因素，维持了残胰腺的再生状态，因为如果将胰大切除术中切除的叶对应的胰管结扎并留在原位，残胰腺的重量只是暂时增加，然后恢复到正常重量。在干细胞研究中，在小鼠胚胎干细胞分化研究中获得的神经元样细胞被发现可以改善模型大鼠帕金森病的症状。研究了骨髓源性细胞和胰管上皮细胞向胰岛细胞的分化以及骨髓细胞与胰岛细胞的电细胞融合，为今后的研究积累了有趣的知识。