Eliminating residual undifferentiated cells from iPSC-CMs for safer clinical application of iPSCs

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K10211
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular surgery
• Research Institution: Osaka University
• Principal Investigator: Masuda Shigeo 大阪大学, 医学系研究科, 特任准教授(常勤) (10396749)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ヒトiPS細胞 / 造腫瘍性 / 未分化細胞除去 / 分子標的治療薬

Outline of Final Research Achievements

Clinical application of iPS-derived cardiomyocytes (iPS-CMs) is considered to be one of the most promising approach to regenerative treatment for severe heart failure. However, its success would largely depend on safety, including prevention of tumor formation (Masuda S, et al. Nature Rev Cardiol. 2014;11:553-4). Here, we demonstrate that BET protein bromodomain antagonist is efficacious in removing residual undifferentiated cells in vitro. In this context, it was revealed that BET protein antagonist functions as a Nanog inhibitor within human iPS cells. Furthermore, co-treatment with BET protein antagonist and CDK inhibitors (CDK9 or CDK1 inhibitor) synergistically eliminated residual undifferentiated cells among human iPS-CMs. These findings imply that combination treatment in vitro with these drugs contributes to molecular-targeted treatment on “human iPS cells”.

Free Research Field

再生医療