Biomarkers for Diabetes Using Stem Cell-Derived Beta Cells

描述（由申请人提供）：1型糖尿病（T1D）的诊断目前受到在相对晚期阶段检测疾病的方法的限制，此时血糖水平升高且自身免疫性攻击正在进行中。到了这个阶段，考虑到目前可用的治疗（胰岛素注射），B细胞损失事实上是不可逆的。在这个晚期阶段之前，早期检测β细胞应激的生物标志物将改善诊断，并开辟新的窗口来监测和治疗疾病。我们将从人多能干细胞中产生功能成熟的、“从未受到应激”的β细胞，并通过离体提供各种应激条件，使用这些细胞来鉴定β细胞应激的最早阶段的生物标志物。此外，我们可以使用来自T1D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：T1D患者的β细胞是否对压力特别敏感，或者在免疫攻击之前有其他方面的缺陷？成功鉴定应激的早期β细胞特异性生物标志物将能够更早地检测和诊断，更好地跟踪从无症状到临床表现的进展，以及对人类T1D的最早阶段和可能的起始事件的更机械的理解。

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.