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Human induced pluripotent stem cell derived cardiomyocyte maturation by DNA integrative free-delivery of key regulators

Research Project

Project/Area Number 20K17078
Research Category

Grant-in-Aid for Early-Career Scientists

Allocation TypeMulti-year Fund
Review Section Basic Section 53020:Cardiology-related
Research InstitutionKyoto University

Principal Investigator

Lucena-Cacace Antonio  京都大学, iPS細胞研究所, 特命助教 (60832748)

Project Period (FY) 2020-04-01 – 2023-03-31
Project Status Completed (Fiscal Year 2022)
Budget Amount *help
¥4,160,000 (Direct Cost: ¥3,200,000、Indirect Cost: ¥960,000)
Fiscal Year 2021: ¥1,820,000 (Direct Cost: ¥1,400,000、Indirect Cost: ¥420,000)
Fiscal Year 2020: ¥2,340,000 (Direct Cost: ¥1,800,000、Indirect Cost: ¥540,000)
KeywordsCardiac maturation / TNNI3 / hiPSC-CM / Stem Cell Research / Cell Cycle / cardiac maturation / tnni3 / small molecules / heart / epicardium / eht / tissue bioengineering / disease modeling / stem cells / cellular bioengineering / nanomedic / hiPSC-EPI / Heart
Outline of Research at the Start

1./ To conduct functional assays to assess cardiac functionality
2./ Elucidation of molecular mechanisms: (1) activation of gene repressors or activators or (2) activation of signaling cascades via kinase phosphorylations
3./ Developing a DNA integrative-free system for key factors delivery.

Outline of Final Research Achievements

We extensively worked in developing safe methods to increase the maturation of hiPSC-derived cardiomyocytes to improve clinical applications in regenerative medicine.

Eventually, we developed methods to increase the adult-like properties of hiPSC-CM that can be transferred to clinical applications.

Academic Significance and Societal Importance of the Research Achievements

We developed methods with clinical applications to increase the maturation of cardiac tissues derived from human iPS exploiting the control of the cardiac cell cycle.

Report

(4 results)
  • 2022 Annual Research Report   Final Research Report ( PDF )
  • 2021 Research-status Report
  • 2020 Research-status Report
  • Research Products

    (8 results)

All 2022 2020 Other

All Journal Article (3 results) (of which Int'l Joint Research: 3 results,  Peer Reviewed: 3 results) Presentation (1 results) (of which Invited: 1 results) Remarks (3 results) Patent(Industrial Property Rights) (1 results) (of which Overseas: 1 results)

  • [Journal Article] Analysis of Transcriptional Profiling of Chamber-Specific Human Cardiac Myocytes Derived from Pluripotent Stem Cells2022

    • Author(s)
      Antonio Lucena-Cacace, Yoshinori Yoshida
    • Journal Title

      Methods Mol Biol

      Volume: 2320 Pages: 219-232

    • DOI

      10.1007/978-1-0716-1484-6_20

    • ISBN
      9781071614839, 9781071614846
    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells2022

    • Author(s)
      Julia Junghof, Yuta Kogure, Tian Yu, Eva Maria Verdugo-Sivianes, Megumi Narita, Antonio Lucena-Cacace, Yoshinori Yoshida
    • Journal Title

      NPJ Regenerative Medicine

      Volume: 7 Issue: 1

    • DOI

      10.1038/s41536-022-00207-w

    • Related Report
      2022 Annual Research Report 2021 Research-status Report
    • Peer Reviewed / Int'l Joint Research
  • [Journal Article] Immunosuppressants Tacrolimus and Sirolimus revert the cardiac antifibrotic properties of p38-MAPK inhibition in 3D-multicellular human iPSC-heart organoids2022

    • Author(s)
      Yu Tian, Yuta Tsujisaka, Vanessa Y Li, Kanae Tani, Antonio Lucena-Cacace, Yoshinori Yoshida
    • Journal Title

      Front Cell Dev Biol

      Volume: 10

    • DOI

      10.3389/fcell.2022.1001453

    • Related Report
      2022 Annual Research Report
    • Peer Reviewed / Int'l Joint Research
  • [Presentation] Maturation of human iPSC-derived cardiomyocytes2022

    • Author(s)
      Antonio Lucena-Cacace
    • Organizer
      Leducq Network: Towards Precision Medicine with Human iPSCs for Cardiac Channelopathies (Stanford University, USA)
    • Related Report
      2022 Annual Research Report
    • Invited
  • [Remarks] 第5回CiRA奨励賞の表彰について

    • URL

      https://www.cira.kyoto-u.ac.jp/j/pressrelease/other/230123-150000.html

    • Related Report
      2022 Annual Research Report
  • [Remarks] CDH18 は胎児期の心外膜細胞の指標であり胎児心外膜から平滑筋細胞の分化を制御している

    • URL

      https://www.cira.kyoto-u.ac.jp/j/pressrelease/news/220209-150000.html

    • Related Report
      2021 Research-status Report
  • [Remarks] 心外膜細胞のバイオマーカーとして CDH18 を同定-CiRA ほか

    • URL

      http://www.qlifepro.com/news/20220214/epicardial-biomarker.html

    • Related Report
      2021 Research-status Report
  • [Patent(Industrial Property Rights)] Mature-cardiomyocyte production method2020

    • Inventor(s)
      Antonio Lucena-Cacace, etc
    • Industrial Property Rights Holder
      Antonio Lucena-Cacace, etc
    • Industrial Property Rights Type
      特許
    • Filing Date
      2020
    • Acquisition Date
      2021
    • Related Report
      2021 Research-status Report
    • Overseas

URL: 

Published: 2020-04-28   Modified: 2025-01-30  

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