Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells
Reversal of diabetes with insulin-producing cells derived in vitro from human pluripotent stem cells
复制标题
DOI：
10.1038/nbt.3033
复制
发表时间：
2014-11-01
影响因子：
46.9
通讯作者：
Kieffer, Timothy J.
中科院分区：
文献类型：
--
作者：
Rezania, Alireza;Bruin, Jennifer E.;Kieffer, Timothy J.
移植胰腺祖细胞或来源于人胚胎干细胞（hESC）的胰岛素分泌细胞已被提议作为糖尿病的治疗。我们描述了一个七阶段的协议，有效地将hESC转化为胰岛素产生细胞。阶段（S）7细胞表达成熟胰腺β细胞的关键标志物，包括MAFA，并且在体外静态孵育期间显示出与人胰岛相似的葡萄糖刺激的胰岛素分泌。使用单细胞成像和动态葡萄糖刺激试验进行的其他表征显示了S7胰岛素分泌细胞和原代人β细胞之间的相似性，但也存在显著差异。然而，S7细胞在40天内迅速逆转了小鼠的糖尿病，比胰腺祖细胞快大约4倍。因此，尽管S7细胞并不等同于成熟的β细胞，但其葡萄糖响应性胰岛素分泌和体内快速逆转糖尿病的能力使其成为胰腺祖细胞或尸体胰岛治疗糖尿病的有希望的替代品。
Transplantation of pancreatic progenitors or insulin-secreting cells derived from human embryonic stem cells (hESCs) has been proposed as a therapy for diabetes. We describe a seven-stage protocol that efficiently converts hESCs into insulin-producing cells. Stage (S) 7 cells expressed key markers of mature pancreatic beta cells, including MAFA, and displayed glucose-stimulated insulin secretion similar to that of human islets during static incubations in vitro. Additional characterization using single-cell imaging and dynamic glucose stimulation assays revealed similarities but also notable differences between S7 insulin-secreting cells and primary human beta cells. Nevertheless, S7 cells rapidly reversed diabetes in mice within 40 days, roughly four times faster than pancreatic progenitors. Therefore, although S7 cells are not funk equivalent to mature beta cells, their capacity for glucose-responsive insulin secretion and rapid reversal of diabetes in vivo makes them a promising alternative to pancreatic progenitor cells or cadaveric islets for the treatment of diabetes.