Insulin production by human embryonic stem cells
Insulin production by human embryonic stem cells
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DOI：
10.2337/diabetes.50.8.1691
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发表时间：
2001-08-01
期刊：
影响因子：
7.7
通讯作者：
Tzukerman, M
中科院分区：
文献类型：
--
作者：
Assady, S;Maor, G;Tzukerman, M
1型糖尿病通常是由胰岛β细胞的自身免疫性破坏引起的，从而导致绝对胰岛素缺乏并完全依赖外源性胰岛素治疗。胰腺或胰岛同种异体移植捐赠的相对缺乏促使人们寻找β细胞替代疗法的替代来源。在目前的研究中，我们使用多能未分化的人胚胎干（hES）细胞作为谱系特异性分化的模型系统。在贴壁和悬浮培养条件下使用hES细胞，我们观察到自发的体外分化，其包括具有产生胰岛素的β细胞特征的细胞的产生。在令人惊讶的高百分比细胞中观察到胰岛素的免疫组织化学染色。以分化依赖性方式观察到胰岛素分泌到培养基中，并且与其他β细胞标志物的出现相关。这些发现验证了hES细胞模型系统作为富集人β细胞或其前体的潜在基础，作为糖尿病细胞替代疗法的可能未来来源。
Type 1 diabetes generally results from autoimmune destruction of pancreatic islet beta -cells, with consequent absolute insulin deficiency and complete dependence on exogenous insulin treatment. The relative paucity of donations for pancreas or islet allograft transplantation has prompted the search for alternative sources for beta -cell replacement therapy. In the current study, we used pluripotent undifferentiated human embryonic stem (hES) cells as a model system for lineage-specific differentiation. Using hES cells in both adherent and suspension culture conditions, we observed spontaneous in vitro differentiation that included the generation of cells with characteristics of insulin-producing beta -cells. Immunohistochemical staining for insulin was observed in a surprisingly high percentage of cells. Secretion of insulin into the medium was observed in a differentiation-dependent manner and was associated with the appearance of other beta -cell markers. These findings validate the hES cell model system as a potential basis for enrichment of human beta -cells or their precursors, as a possible future source for cell replacement therapy in diabetes.