Generation of human iPS-derived pancreatic beta cells and its application towards regenerative medicine

2016 Fiscal Year Final Research Report

• Project/Area Number: 26253059
• Research Category: Grant-in-Aid for Scientific Research (A)
• Allocation Type: Single-year Grants
• Section: 一般
• Research Field: Metabolomics
• Research Institution: Tokyo Institute of Technology
• Principal Investigator: Kume Shoen 東京工業大学, 生命理工学院, 教授 (70347011)
• Co-Investigator(Kenkyū-buntansha): 荒木 喜美 熊本大学, 学内共同利用施設等, 教授 (90211705)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: 多能性幹細胞 / 分化誘導 / 糖尿病 / 再生医療 / 膵臓 / 代謝 / 増殖 / モノアミン

Outline of Final Research Achievements

Through screening and analysis of small molecular compound that potentiated differentiation of human induced pluripotent stem (hiPS) cells into pancreatic beta cells, we found that activation of Wnt signal increased beta cell differentiation in hiPS cells, and that our previously identified VMAT2-monoamine as a negative regulator for pancreatic differentiation, also applied to hiPS cells. We also identified domperidone (DPD), a dopamine D2 receptor (DRD2) antagonist, as a compound that enhances beta cell mass. In adult islet dissociation cultures, beta cell loss occurs through dedifferentiation, which was prevented by DPD. Dopamine modulates beta cell mass through DRD2 and exerts an inhibitory effect on adenosine signaling, a previously identified beta cell mass positive regulator. We believe that our knowledge on regulation of beta cell differentiation and cell mass regulation would be profitable for future manipulation of hiPS-derived beta cells.

Free Research Field

代謝内分泌学