以間葉系幹細胞再生胰島的策略探討

Abstract

糖尿病為本世紀最嚴重的流行疾病。糖尿病病患因為胰島細胞的喪失或是功能不全，而導致無法調降血液中血糖濃度，因此能夠恢復胰島的數量以及其功能對於患者來說是一個必要的治療幫助。現今在移植胰島方面的最大的瓶頸為胰島數量不足，因此我們希望嘗試使用病患自體幹細胞進行分化成類胰島細胞，再移植進病患體內以幫助治療。我們使用間葉系幹細胞進行研究，在口腔中即有多種間葉系幹細胞且取得容易傷口小恢復速度佳，是進行幹細胞分化研究的最佳來源。近五年有約三百多篇的論文期刊討論了如何將幹細胞分化成類胰島細胞團，但討論的重點多放在會分泌胰島素的β細胞分化上，而忽略了在胰島細胞團中的其他細胞，包括：α細胞、ε細胞、δ細胞以及PP細胞。在本研究中，我們著重於三個重點，其一，我們的預期分化出完整的類胰島細胞，亦即包含全部種類的不同細胞，使其細胞組成與比例相似於人類胰島細胞；其二，我們利用甲殼素使細胞不易貼附的特性，重新建立胰島細胞團的球型架構；其三，檢測製作出的類胰島細胞可以正常進行功能，各細胞分泌不同的激素且能夠調控血糖。此類胰島細胞的分化若能應用於臨床，即能為將來的再生醫學以及移植上提供幫助，穩定提供類胰島細胞來源。

Diabetes is the most serious disease this century. Diabetes patients are unable to regulate their blood sugar level because of the loss of islets or islet dysfunction, it is necessary to recover their islet number and functions. Nowadays, the biggest bottleneck in islet transplantation is insufficient number of islets, thus we tried to use autologous stem cells of patients to differentiate into islet-like cells, and used in transplantation to help curing diabetes. In our research, we use mesenchymal stem cells. There is a variety of mesenchymal stem cells in mouth, easily to get, the wound is small and recover fast, which is the best source for investigation. In the last five years, there are about three hundred papers studied about how to differentiate stem cells into islet-like cells, but they only discussed about differentiate into β cells, which secrete insulin, and ignore the rest of the cells in human islets of Langerhans, including α cells, ε cells, δ cells, and PP cells. In our research, we focus on three key points: first, we expect to differentiate complete islet-like cells, which the cells in the clusters’ composite and ratio are similar to human islets; second, we rebuild the sphere structure of islet on chitosan, which have the characteristic that the cells are unattached on it; third, to test the produced islet-like cells’ function, different cells can secrete different hormones and the clusters can regulate the blood sugar level. We expect that the differentiation of islet could be used in clinic, and contribute to regenerative medicine and transplantation, provide a stable source of pancreatic islet cells.