Biomarkers for Diabetes Using Stem Cell-Derived Beta Cells

描述（由申请人提供）：目前，1型糖尿病（T1D）的诊断受限于在相对较晚阶段检测疾病的方法，此时血糖水平升高，自身免疫攻击正在进行中。在这个阶段，鉴于目前可用的治疗方法（胰岛素注射），b细胞的损失事实上是不可逆转的。早期检测β细胞应激的生物标志物，在这一晚期阶段之前，将改善诊断，并为监测和可能的治疗疾病打开新的窗口。我们将从人类多能干细胞中产生功能成熟、“从未受到压力”的β细胞，并通过提供各种体外应激条件，利用这些细胞识别β细胞应激早期阶段的生物标志物。此外，我们可以使用来自T1D患者和对照患者的干细胞来研究他们对压力的β细胞反应的差异。换句话说，我们可以问：在免疫攻击之前，T1D患者的β细胞是否对压力特别敏感或以其他方式存在缺陷？成功鉴定早期β细胞特异性应激生物标志物将有助于早期检测和诊断，更好地跟踪从无症状到临床表现的进展，并对人类T1D的早期阶段和可能的启动事件有更深入的了解。

DESCRIPTION (provided by applicant): The diagnosis of Type 1 diabetes (T1D) is currently limited by methods that detect the disease at relatively late stages, when blood glucose levels rise and autoimmune attack is well underway. By this stage, given the treatments presently available (insulin injection), the b cell loss is de facto, irreversible. Biomarkers for early detetion of β cell stress, before this late stage, would improve diagnosis and open up new windows to monitor and possibly treat the disease. We will produce functionally mature, "never-before-stressed", β cells from human pluripotent stem cells and use these cells to identify biomarkers for the earliest stages of β cell stress by providing various stress conditions ex vivo. In additin, we can use stem cells from T1D and control patients to investigate differences in their β ell responses to stress. In other words, we can ask: are β cells in T1D patients especially sensitive to stress or in other ways defective before an immune attack? Successful identification of early β ell-specific biomarkers for stress will enable earlier detection and diagnosis, better tracking f progress from asymptomatic to clinical presentation, and a more mechanistic understanding of the earliest stages and possibly initiating events of human T1D.