miRNA-302 facilitates reprogramming of human adult hepatocytes into pancreatic islets-like cells in combination with a chemical defined media
miRNA-302 facilitates reprogramming of human adult hepatocytes into pancreatic islets-like cells in combination with a chemical defined media
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miRNA-302 与化学成分确定培养基相结合，促进人类成年肝细胞重编程为胰岛样细胞
DOI：
10.1016/j.bbrc.2014.09.095
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发表时间：
2014-10-24
影响因子：
3.1
通讯作者：
Tan, Jianming
中科院分区：
文献类型：
--
作者：
Lu, Jun;Dong, Huiyue;Tan, Jianming
再生疗法需要将一种细胞类型直接转化为另一种细胞类型，而无需中间多能阶段。腹侧胰腺和肝脏具有共同的发育起源。最近的研究表明，肝细胞可以被诱导转分化为产生胰岛素的细胞。在本文中，我们展示了一种新策略，可以实现将人肝细胞直接转化为替代β细胞。用 microRNA-302 (miR-302) 模拟物和 Pdx1、Ngn3 和 MafA 表达质粒转染肝细胞，然后使用化学限定的培养系统使胰岛素分泌细胞成熟。 miR-302 模拟物的共转染增加了胰腺发育相关基因（Sox17、Foxa2 和内源性 Pdx1）的转录。此外，在治疗结束时，肝细胞变成胰岛素表达细胞，在体外响应生理葡萄糖变化而释放激素。这项工作表明，miR-302 的参与可能促进成体肝细胞向胰岛样细胞的转化。 (C) 2014 Elsevier Inc. 保留所有权利。
The direct conversion of one cell type to another without an intermediate pluripotent stage is required for regenerative therapies. The ventral pancreas and liver share a common developmental origin. Recent studies have shown that hepatocytes could be induced to transdifferentiate into insulin-producing cells. In this paper, we showed a new strategy to achieve the direct conversion of human hepatocytes into surrogate beta cells. Hepatocytes were transfected with microRNA-302 (miR-302) mimic and Pdx1, Ngn3 and MafA expressed plasmids, followed by a chemical-defined culture system for maturation of insulin-secreting cells. Co-transfection of miR-302 mimic increased the transcription of pancreatic development-related genes (Sox17, Foxa2, and endogenous Pdx1). Furthermore, at the end of this treatment, hepatocytes became insulin expressed cells that released the hormone in response to a physiological glucose change in vitro. This work shows that miR-302 participation may facilitates the conversion of adult hepatocytes into pancreatic islets-like cells. (C) 2014 Elsevier Inc. All rights reserved.