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Generation of insulin-producing β-like cells from human iPS cells in a defined and completely xeno-free culture system 被引量:6

Generation of insulin-producing β-like cells from human iPS cells in a defined and completely xeno-free culture system
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摘要 因为他们的区别能力,人的导致的 pluripotent 茎(臀部) 细胞为生产胰岛素的胰腺的细胞的产生被认为潜在的来源。在这研究,我们开发了一个五步的 xeno 免费的文化系统高效地在 vitro 区分臀部房间进生产胰岛素的房间。我们发现高少量集中为明确地首先导致区别进胰腺、十二指肠的 homeobox-1 (PDX1 ) 是关键的积极胰腺的祖先然后进 neurogenin 3 (NGN3 ) 表示胰腺的内分泌的祖先,当压制区别进肝或肠的房间时。我们也发现 3-isobutyl-1-methylxanthine (IBMX ) 的联合, exendin-4,和菸碱为进胰岛素的区别是重要的表示了各种各样的胰腺的房间标记的单人赛积极的房间。最尤其是,区分的房间包含了响应各种各样的胰岛素促泌素和葡萄糖的高水平被释放的内长的 C 肽水池。因此,我们的结果表明在 xeno 免费的条件下面产生导出臀部的胰腺的房间的可行性并且加亮他们的潜力与类型 1 糖尿病对待病人。 Human induced pluripotent stem (hiPS) cells are considered a potential source for the generation of insulin-producing pancreatic β-ceUs because of their differentiation capacity. In this study, we have developed a five-step xeno-free culture system to efficiently dif- ferentiate hiPS cells into insulin-producing cells in vitro. We found that a high NOGGIN concentration is crucial for specifically inducing the differentiation first into pancreatic and duodenal homeobox-1 (PDX1)-positive pancreatic progenitors and then into neurogenin 3 (NGN3)-expressing pancreatic endocrine progenitors, while suppressing the differentiation into hepatic or intestinal cells. We also found that a combination of 3-isobutyl-l-methylxanthine (IBMX), exendin-4, and nicotinamide was important for the differentiation into insulin single-positive cells that expressed various pancreatic β-cell markers. Most notably, the differentiated cells contained en- dogenous C-peptide pools that were released in response to various insulin secretagogues and high levels of glucose. Therefore, our results demonstrate the feasibility of generating hiPS-derived pancreatic β-ceUs under xeno-free conditions and highlight their poten- tial to treat patients with type I diabetes.
出处 《Journal of Molecular Cell Biology》 SCIE CAS CSCD 2014年第5期394-408,共15页 分子细胞生物学报(英文版)
关键词 胰岛素分泌 细胞分化 培养系统 异物 IPS 分化能力 NOGGIN HIPS diabetes, pancreas, ceil therapy, hiPS ceils, xeno-free differentiation, β-cells
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