Direct differentiation of hepatic stem-like WB cells into insulin-producing cells using small molecules.

Direct differentiation of hepatic stem-like WB cells into insulin-producing cells using small molecules.
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使用小分子将肝干样 WB 细胞直接分化为胰岛素产生细胞

DOI:
10.1038/srep01185
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发表时间:
2013
期刊:
影响因子:
4.6
通讯作者:
Han, Weidong
Han, Weidong
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Liu, Jianping;Liu, Yanmei;Wang, Honggang;Hao, Haojie;Han, Qingwang;Shen, Jing;Shi, Jun;Li, Chunlin;Mu, Yiming;Han, Weidong

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最近的证据表明,实验性诱导肝细胞转化为胰腺细胞为1型糖尿病提供了新的细胞移植治疗前景。从大鼠肝上皮干细胞样WB-F344细胞(WB细胞)逐步分化为功能性胰岛素分泌细胞将确定β细胞发育的关键步骤,并可能被证明可用于糖尿病患者的移植治疗。该方案中的一个重要步骤是基于5-氮杂-2 ′-脱氧胞苷、胰蛋白酶抑制剂A、视黄酸和胰岛素、转铁蛋白和亚硒酸盐的混合物的组合的诱导产生表达Pdx 1的胰腺前体细胞。表达Pdx 1的细胞表达其他胰腺标志物,并在体外和体内促进内分泌细胞。这项研究表明了一种有效的化学方案,利用小分子将WB细胞分化为功能性胰岛素产生细胞,并代表了一种有前途的基于肝细胞的糖尿病治疗方法。
Recent evidence suggests that experimental induction of hepatocytes into pancreatic cells provides new cell transplantation therapy prospects for type 1 diabetes mellitus. Stepwise differentiation from rat liver epithelial stem-like WB-F344 cells (WB cells) into functional insulin-secreting cells will identify key steps in β-cell development and may yet prove useful for transplantation therapy for diabetic patients. An essential step in this protocol was the generation of pancreatic precursor cell that express Pdx1 based on induction by a combination of 5-aza-2′-deoxycytidine, trichostatin A, retinoic acid and a mix of insulin, transferrin and selenite. The Pdx1-expressing cells express other pancreatic markers and contribute to endocrine cellsin vitroandin vivo. This study indicates an efficient chemical protocol for differentiating WB cells into functional insulin-producing cells using small molecules and represents a promising hepatocyte-based treatment for diabetes mellitus.
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