Sakano Daisuke, Shiraki Nobuaki, Kume Shoen
Department of Stem Cell Biology, Institute of Molecular Embryology and Genetics (IMEG), Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto, 860-0811, Japan.
Program for Leading Graduate Schools "HIGO (Health life science; Interdisciplinary and Glocal Oriented) Program", Kumamoto University, Honjo 2-2-1, Chuo-ku, Kumamoto, 860-0811, Japan.
Methods Mol Biol. 2016;1341:417-23. doi: 10.1007/7651_2015_217.
Pluripotent stem cells are considered as a cell source for replacement therapies for pancreatic beta cells and other organs.We identified tetrabenazine (TBZ), vesicular monoamine transporter 2 (VMAT2) inhibitor as a promoter of late-stage differentiation of Pdx1-positive pancreatic progenitor cells into Ngn3-positive endocrine progenitor cells. A cell-permeable cAMP analog, dBu-cAMP promotes beta cell maturation in late stage of differentiation. The induced beta cells can secrete insulin in a glucose-dependent manner.Our protocol consists of a three -step differentiation process. ES cell recapitulate embryonic developmental processes in vitro. Therefore, the ES cell differentiation system is a useful model for the understanding of molecular mechanism of beta-cell differentiation and are useful for application for future regenerative medicine.
多能干细胞被视为用于胰腺β细胞和其他器官替代疗法的细胞来源。我们确定了囊泡单胺转运体2（VMAT2）抑制剂丁苯那嗪（TBZ）是Pdx1阳性胰腺祖细胞晚期分化为Ngn3阳性内分泌祖细胞的促进剂。一种细胞可渗透的环磷酸腺苷（cAMP）类似物二丁酰环磷腺苷钙（dBu-cAMP）在分化后期促进β细胞成熟。诱导产生的β细胞能够以葡萄糖依赖的方式分泌胰岛素。我们的方案包括一个三步分化过程。胚胎干细胞在体外重现胚胎发育过程。因此，胚胎干细胞分化系统是理解β细胞分化分子机制的有用模型，对未来再生医学的应用也很有用。
