探討胰島移植中優化分離與篩選之方法

Abstract

全世界約有四億多人罹患糖尿病，其中10%為甲型糖尿病患，是因自體免疫疾病導致胰島細胞缺損而無法分泌足夠的胰島素；90%則是乙型糖尿病是因細胞對胰島素不敏感的胰島素抗性所導致。目前糖尿病的治療方式之一是大體胰島移植，主要應用在甲型糖尿病患者幫助其重新恢復調控血糖恆定的能力。但目前尚未出現有效的方法控制移植的胰島品質，再加上如血管栓塞等其餘的手術後併發因素，導致有約30%的病人會需要在3個月內重新進行移植手術。因此本研究欲建立一個能夠篩選胰島品質的系統，可望在臨床醫療上對於胰島品質的篩選有所貢獻。本實驗預期利用FluoZin™-3鋅離子螢光染劑，配合鋅離子螯合螢光指示劑以偵測與胰島素結合在一起的鋅離子。藉由以上系統挑選對於葡萄糖刺激有正常分泌反應的健康胰島細胞再予以移植入病患體內以提高手術成功率及預後情形。除了挑選一般胰島品質外，此系統也可應用在挑選自體幹細胞生成之胰島相似細胞簇，可去除胰島移植的排斥作用。但此種治療方式仍在發展階段，利用本系統可篩選出具有正常胰島功能的細胞簇，將有助於此種新興療法發展。

Diabetes is a common metabolic disease all over the world. According to statistics from International Diabetes Federation, there is 415 million people with diabetes until 2015. Approximately 90% of diabetes patients are type2 diabetes, while 10% are type 1, which is due to autoimmune problem and result in pancreatic islet cell loss. One of eye-catching therapy to Type 1 diabetes is pancreatic islet transplantation. Although pancreatic islet transplantation become hopeful since it is reported that it can help patients reach insulin independent, it remain quite lots of problems such as shortage of source of islet, low survival rate of transplanted islets and immune risk of allograft. Also, present procedure of islet transplantation does not screen islet function individually, so there might be some functionless tissue transplanted to the recipient unintentional, and that’ll cause more risk to the recipient. So in this study, we tried to establish a rapid functional screen system for islet through detecting insulin cofactor zinc ion instead of detecting insulin itself. In this way we can avoid time consuming step in order to detect protein and high cost of using antibodies. As a result, screening every islets that transplanted to patients become possible. This system also possess the potential to apply in autologous stem cell therapy which is also considered as a promising option to cure type1 diabetes in the future.