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2021 年度 実施状況報告書

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

研究課題

研究課題/領域番号 20K17078
研究機関京都大学

研究代表者

Lucena.Cacace Antonio  京都大学, iPS細胞研究所, 特定研究員 (60832748)

研究期間 (年度) 2020-04-01 – 2023-03-31
キーワードhiPSC-CM / TNNI3 / disease modeling / stem cells / cellular bioengineering / cardiac maturation
研究実績の概要

Currently, we have developed a technology to enhance maturation in cardiomyocytes derived from iPS cells. Our system relies on a scaffold-free, gene-induction-only way by inducing cell-autonomous mechanisms through the forced induction of key factors. In our model, we lead cardiomyocytes to express the ion channels of advanced maturation required for disease modelings, such as those related to ion trafficking (S100A1) or the expression of caveolin-3 (CAV3), necessary for the induction of T-tubules.

現在までの達成度 (区分)
現在までの達成度 (区分)

3: やや遅れている

理由

Some experiments were planned to be conducted internationally in collaborative research. Due to the COVID-19 pandemics, the joint investigation between countries got slightly delayed.

In addition, the assessment of the maturation of our cardiomyocytes requires a multi-layered set of functionality assessments. One of the most time-consuming is electrophysiology which includes Patch-Clamp, a time-consuming experiment that require several repetitions for reliable reproducibility.

今後の研究の推進方策

Currently, we are implementing our maturation system into a cardiac organoid model for reliable preclinical studies of disease modeling. To that end, this fiscal year, we will focus our final efforts on two different aspects; (1) electrophysiological properties assessment and (2) recapitulation of disease modeling by recapitulating electrocardiogram abnormality of cardiomyocytes differentiated from patient-derived iPSC of patients harboring pathological/symptomatic mutations of long QT syndrome (LQTS) or Hutchinson–Gilford progeria syndrome (HGPS)

次年度使用額が生じた理由

Due to the COVID-19 pandemics, most of the research expenses got delayed during the last fiscal year. The amount of budget to be used this fiscal year will be distributed for the acquisition of equipment for electrophysiology properties assessment and laboratory reagents for the production of mature cardiomyocytes.

  • 研究成果

    (5件)

すべて 2022 2020 その他

すべて 雑誌論文 (2件) (うち国際共著 2件、 査読あり 2件) 備考 (2件) 産業財産権 (1件) (うち外国 1件)

  • [雑誌論文] Analysis of Transcriptional Profiling of Chamber-Specific Human Cardiac Myocytes Derived from Pluripotent Stem Cells2022

    • 著者名/発表者名
      Antonio Lucena-Cacace, Yoshinori Yoshida
    • 雑誌名

      Methods Mol Biol

      巻: 2320 ページ: 219-232

    • DOI

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

    • 査読あり / 国際共著
  • [雑誌論文] CDH18 is a fetal epicardial biomarker regulating differentiation towards vascular smooth muscle cells2022

    • 著者名/発表者名
      Julia Junghof, Yuta Kogure, Tian Yu, Eva Maria Verdugo-Sivianes, Megumi Narita, Antonio Lucena-Cacace, Yoshinori Yoshida
    • 雑誌名

      NPJ Regenerative Medicine

      巻: 7 ページ: online

    • DOI

      10.1038/s41536-022-00207-w

    • 査読あり / 国際共著
  • [備考] 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

  • [備考] 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

  • [産業財産権] Mature-cardiomyocyte production method2020

    • 発明者名
      Antonio Lucena-Cacace, etc
    • 権利者名
      Antonio Lucena-Cacace, etc
    • 産業財産権種類
      特許
    • 産業財産権番号
      PCT/JP2021/007466
    • 外国

URL: 

公開日: 2023-12-25  

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