Takeuchi Hiroki, Nakatsuji Norio, Suemori Hirofumi
Department of Embryonic Stem Cell Research, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
1] Institute for Integrated Cell-Material Sciences (WPI-iCeMS), Kyoto University, Ushinomiya-cho, Yoshida, Sakyo-ku, Kyoto 606-8501, Japan [2] Department of Development and Differentiation, Institute for Frontier Medical Sciences, Kyoto University, 53 Kawahara-cho, Shogoin, Sakyo-ku, Kyoto 606-8507, Japan.
Sci Rep. 2014 Mar 27;4:4488. doi: 10.1038/srep04488.
Insulin-producing cells (IPCs) derived from human pluripotent stem cells (hPSCs) may be useful in cell therapy and drug discovery for diabetes. Here, we examined various growth factors and small molecules including those previously reported to develop a robust differentiation method for induction of mature IPCs from hPSCs. We established a protocol that induced PDX1-positive pancreatic progenitor cells at high efficiency, and further induced mature IPCs by treatment with forskolin, dexamethasone, Alk5 inhibitor II and nicotinamide in 3D culture. The cells that differentiated into INSULIN-positive and C-PEPTIDE-positive cells secreted insulin in response to glucose stimulation, indicating a functional IPC phenotype. We also found that this method was applicable to different types of hPSCs.
源自人多能干细胞（hPSC）的胰岛素生成细胞（IPC）可能在糖尿病的细胞治疗和药物发现中有用。在此，我们研究了各种生长因子和小分子，包括那些先前报道的用于开发从hPSC高效诱导成熟IPC的强大分化方法的因子和分子。我们建立了一种方案，该方案能高效诱导PDX1阳性胰腺祖细胞，并在三维培养中通过用福司可林、地塞米松、Alk5抑制剂II和烟酰胺处理进一步诱导成熟IPC。分化为胰岛素阳性和C肽阳性细胞的细胞在葡萄糖刺激下分泌胰岛素，表明具有功能性IPC表型。我们还发现这种方法适用于不同类型的hPSC。
