Glucose responsive insulin production from human embryonic germ (EG) cell derivatives
Glucose responsive insulin production from human embryonic germ (EG) cell derivatives
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DOI：
10.1016/j.bbrc.2007.03.017
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发表时间：
2007-05-11
影响因子：
3.1
通讯作者：
Shamblott, Michael J.
中科院分区：
文献类型：
--
作者：
Clark, Gregory O.;Yochem, Robert L.;Shamblott, Michael J.
I型糖尿病使数百万人每天承受疾病管理、危及生命的低血糖和长期并发症如视网膜病变、肾病、心脏病和中风的负担。提供葡萄糖调节的胰岛素供应的细胞移植疗法已在临床上实施，但受到安全性、有效性和供应考虑的限制。干细胞为移植治疗提供了丰富而灵活的细胞来源。在这里，我们表明，来自人胚胎生殖（EG）细胞的细胞表达的标志物定形内胚层，胰腺和β细胞的发展，葡萄糖传感，并生产成熟的胰岛素。这些细胞整合了葡萄糖应答调节前胰岛素原mRNA和体外胰岛素C肽表达所必需的功能。移植到小鼠体内后，细胞变得胰岛素和C肽免疫反应性，并产生血浆C肽响应葡萄糖。这些发现表明，EG细胞衍生物可能最终作为胰岛素产生细胞的来源，用于治疗糖尿病。(c)2007爱思唯尔公司All rights reserved.
Type I diabetes mellitus subjects millions to a daily burden of disease management, life threatening hypoglycemia and long-term complications such as retinopathy, nephropathy, heart disease, and stroke. Cell transplantation therapies providing a glucose-regulated supply of insulin have been implemented clinically, but are limited by safety, efficacy and supply considerations. Stem cells promise a plentiful and flexible source of cells for transplantation therapies. Here, we show that cells derived from human embryonic germ (EG) cells express markers of definitive endoderm, pancreatic and beta-cell development, glucose sensing, and production of mature insulin. These cells integrate functions necessary for glucose responsive regulation of preproinsulin mRNA and expression of insulin C-peptide ill vitro. Following transplantation into mice, cells become insulin and C-peptide immunoreactive and produce plasma C-peptide in response to glucose. These findings suggest that EG cell derivatives may eventually serve as a source of insulin producing cells for the treatment of diabetes. (c) 2007 Elsevier Inc. All rights reserved.