Generation of stem cell-derived β-cells from patients with type 1 diabetes.
Generation of stem cell-derived β-cells from patients with type 1 diabetes.
复制标题
1型糖尿病患者的干细胞衍生的β细胞产生。
DOI：
10.1038/ncomms11463
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发表时间：
2016-05-10
影响因子：
16.6
通讯作者：
Melton DA
中科院分区：
文献类型：
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作者：
Millman JR;Xie C;Van Dervort A;Gürtler M;Pagliuca FW;Melton DA
我们近期报道了功能性干细胞衍生的β细胞（SC -β细胞）的可规模化体外生产。在此，我们将这一方法拓展到从1型糖尿病患者（T1D）中产生首批SC -β细胞。在1型糖尿病疾病进展过程中，β细胞遭到破坏，这使得过去难以对其进行广泛研究。这些1型糖尿病SC -β细胞表达β细胞标志物，在体外和体内都对葡萄糖有反应，能预防小鼠的四氧嘧啶诱导的糖尿病，并且对降糖药物有反应。此外，我们利用一种体外疾病模型证明这些细胞对不同形式的β细胞应激有反应。通过这些检测，我们发现1型糖尿病SC -β细胞与来自非糖尿病患者的SC -β细胞相比没有重大差异。这些结果表明，1型糖尿病SC -β细胞有可能用于糖尿病治疗、药物筛选以及β细胞生物学研究。
胰腺β细胞可由多能干细胞产生。在此，作者表明，来自1型糖尿病患者的人类诱导多能干细胞可分化为类β细胞，与来自非糖尿病个体的细胞相比没有可检测到的差异。
We recently reported the scalable in vitro production of functional stem cell-derived β-cells (SC-β cells). Here we extend this approach to generate the first SC-β cells from type 1 diabetic patients (T1D). β-cells are destroyed during T1D disease progression, making it difficult to extensively study them in the past. These T1D SC-β cells express β-cell markers, respond to glucose both in vitro and in vivo, prevent alloxan-induced diabetes in mice and respond to anti-diabetic drugs. Furthermore, we use an in vitro disease model to demonstrate the cells respond to different forms of β-cell stress. Using these assays, we find no major differences in T1D SC-β cells compared with SC-β cells derived from non-diabetic patients. These results show that T1D SC-β cells could potentially be used for the treatment of diabetes, drug screening and the study of β-cell biology. Pancreatic β cells can be generated from pluripotent stem cells. Here, the authors show that human induced pluripotent stem cells from patients with type 1 diabetes can be differentiated into β-like cells that have no detectable differences compared with cells from non-diabetic individuals.