Investigation of maturation mechanism of iPS cell-derived cardiac micro tissue by metabolic switch.

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K22949
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0905:Surgery of the organs maintaining homeostasis and related fields
• Research Institution: Kyoto University
• Principal Investigator: Murata Kozue 京都大学, 医学研究科, 助教 (80884329)
• Project Period (FY): 2020-09-11 – 2022-03-31
• Keywords: 心臓 / iPS細胞 / マイクロ心臓組織 / 成熟化 / 脂肪酸 / 脂質代謝

Outline of Final Research Achievements

Regenerative medicine and drug discovery research using human iPS cells must overcome the problem of immaturity of differentiated cells. We focused on the importance of the metabolic switch in the maturation of human iPS cell-derived cardiomyocytes, in which energy production mainly changes from glucose metabolism to fatty acid metabolism. We investigated whether 3D microcardiac tissue (CMT) could be matured to a level applicable to clinical applications by culturing CMT in the presence of fatty acids. The results showed that the expression of CD36 was promoted by the combination of various fatty acids such as palmitic acid, oleic acid, and linolenic acid, Dexamethazone, T3 hormone, and PPARA agonist.　Under these conditions, responsiveness to electrical stimulation showed a maturation trend.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

我々の独自のiPS由来3Dマイクロ心臓組織は心筋細胞以外の多種心臓構成細胞で構成されている。心筋細胞以外の多種心臓構成細胞で構成されている組織を、脂肪酸添加をはじめとする複合的刺激の下で培養した際の挙動に関する知見はこれまで報告されていない。本研究により人工心臓組織の成熟に関わる新たな知見を提唱することができた。一方、本研究の目的である、人工心臓組織を成熟化させる方法の確立には、物理的刺激の併用などさらなる因子が必要であることも示唆された。