公开(公告)号：US20150159140A1

公开(公告)日：2015-06-11

申请号：US14453799

申请日：2014-08-07

Applicant: KOREA ADVANCED INSTITUTE OF SCIENCE AND TECHNOLOGY

Inventor： Yong-mahn HAN ,  Young-jin KIM

IPC: C12N5/071 ,  A61K35/39 ,  G01N33/50 ,  C07K14/62

CPC classification number: C12N5/0677 ,  A61K35/39 ,  A61K35/545 ,  C07K14/62 ,  C12N2500/12 ,  C12N2500/38 ,  C12N2501/01 ,  C12N2501/115 ,  C12N2501/15 ,  C12N2501/155 ,  C12N2501/16 ,  C12N2501/335 ,  C12N2501/385 ,  C12N2501/41 ,  C12N2501/415 ,  C12N2501/727 ,  C12N2506/02 ,  C12N2506/45 ,  G01N33/507 ,  G01N2500/10

Abstract: The present invention prepared insulin-producing endocrine cells by inducing the differentiation of human embryonic stem cells or human induced pluripotent stem cells into definitive endoderm (DE), pancreatic endoderm (PE), endocrine progenitors (EP), and endocrine cells (EC) stepwise in that order. Particularly, the present invention established the conditions for the formation of an insulin producing endocrine aggregate (EA) from the endocrine cells. Especially in this invention, it was confirmed that the endocrine aggregate has the cell proliferation potential at a significant level and has the increased insulin productivity as well as the activity of inhibiting cell necrosis and apoptosis. Therefore, the method for preparing the endocrine aggregate of insulin-producing beta cells from human pluripotent stem cells can be effectively used for the examination of the medicinal effect of the conventional antidiabetic agents and of the novel antidiabetic drugs.

Abstract translation: 本发明通过诱导将人胚胎干细胞或人诱导的多能干细胞分化为定形内胚层（DE），胰内胚层（PE），内分泌祖细胞（EP）和内分泌细胞（EC）逐步分化来制备产生胰岛素的内分泌细胞 以该顺序。 特别地，本发明建立了从内分泌细胞形成胰岛素产生内分泌骨料（EA）的条件。 特别是在本发明中，证实内分泌骨料具有显着水平的细胞增殖潜力，胰岛素生产力增加以及抑制细胞坏死和细胞凋亡的活性。 因此，能够有效地利用来自人多能干细胞的胰岛素生成β细胞内分泌聚集体的制备方法，用于检测常规抗糖尿病药和新型抗糖尿病药物的药效。