Construction and mechanicsm analysis of HCM model using maturated 3D heart tissue

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K16218
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 49030:Experimental pathology-related
• Research Institution: Kyoto University
• Principal Investigator: Fujiwara Yuya 京都大学, iPS細胞研究所, 特定研究員 (70842912)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: iPS細胞 / iPS細胞由来心筋細胞 / 肥大型心筋症 / 人工組織 / 成熟化

Outline of Final Research Achievements

Hypertrophic cardiomyopathy is a disease with hypertrophy of cardiomyocytes. Although genetic mutation cause HCM, the onset mechanisms are still unclear. We hypothesized that 3D heart tissues maturation manifest HCM phenotypes and these are enable to analyze onset of HCM.
3D heart tissues were maturated by the combination with T112 and mechanical stretching. 3D heart tissues with MYH7 R719Q and MYBPC3 G115* were manifested HCM phenotypes by this maturation method. Moreover, using RNA-seq, we defined signal pathways which were up-regulated in HCM models and inhibition of one of the signal pathway decreased hypertrophic phenotypes.

Free Research Field

細胞生物学

Academic Significance and Societal Importance of the Research Achievements

肥大型心筋症 (HCM) はサルコメア関連遺伝子上の遺伝子変異が原因とされているが、その作用機序は不明であり、有用な治療法はない。そのため、本研究により、試験管内でHCMモデルを構築できたことは解析の簡便さを向上させることで、作用機序の解析を容易にし、また治療薬候補の評価にもつながるものである学術的に価値のある成果である。また本モデルにより、HCMに関与するシグナル伝達経路を同定できたことはHCMの疾患理解につながる社会的意義の大きい研究成果である。