Artifactual insulin release from differentiated embryonic stem cells
Artifactual insulin release from differentiated embryonic stem cells
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DOI：
10.2337/diabetes.53.10.2603
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发表时间：
2004-10-01
期刊：
影响因子：
7.7
通讯作者：
Serup, P
中科院分区：
文献类型：
--
作者：
Hansson, M;Tonning, A;Serup, P
最近的一些报道声称，通过表达巢蛋白的祖细胞的分化，从胚胎干细胞产生胰岛素产生细胞。在这里，我们进一步研究这些含胰岛素细胞的特性。我们发现，虽然分化的细胞含有免疫反应性胰岛素，它们不包含胰岛素原衍生的C-肽。此外，我们发现这些细胞在葡萄糖添加后释放可变的胰岛素，但从未检测到C肽释放。此外，许多胰岛素免疫反应细胞正在经历凋亡或坏死。我们进一步表明，在磷酸肌醇3-激酶抑制剂的存在下培养的细胞，这以前被报道，以促进胰岛素（+）细胞的分化，是不是C-肽免疫反应，但从培养基中摄取荧光素异硫氰酸酯标记的胰岛素。总之，这些数据表明巢蛋白（+）祖细胞产生含有胰岛素的细胞群，不是生物合成的结果，而是外源性胰岛素的摄取。我们的结论是，C-肽的生物合成和分泌，应证明索赔胚胎干细胞后代的胰岛素生产。
Several recent reports claim the generation of insulin-producing cells from embryonic stem cells via the differentiation of progenitors that express nestin. Here, we investigate further the properties of these insulin-containing cells. We find that although differentiated cells contain immunoreactive insulin, they do not contain proinsulin-derived C-peptide. Furthermore, we find variable insulin release from these cells upon glucose addition, but C-peptide release is never detected. In addition, many of the insulin-immunoreactive cells are undergoing apoptosis or necrosis. We further show that cells cultured in the presence of a phosphoinositide 3-kinase inhibitor, which previously was reported to facilitate the differentiation of insulin(+) cells, are not C-peptide immunoreactive but take up fluorescein isothiocyanate-labeled insulin from the culture medium. Together, these data suggest that nestin(+) progenitor cells give rise to a population of cells that contain insulin, not as a result of biosynthesis but from the uptake of exogenous insulin. We conclude that C-peptide biosynthesis and secretion should be demonstrated to claim insulin production from embryonic stem cell progeny.