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Development of novel transplantation method for human iPS cell-derived cardiomyocytes

Research Project

Project/Area Number 21K16084
Research Category

Grant-in-Aid for Early-Career Scientists

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

Principal Investigator

Kobayashi Hideki  信州大学, 医学部附属病院, 助教(診療) (90794389)

Project Period (FY) 2021-04-01 – 2024-03-31
Project Status Completed (Fiscal Year 2023)
Budget Amount *help
¥4,550,000 (Direct Cost: ¥3,500,000、Indirect Cost: ¥1,050,000)
Fiscal Year 2023: ¥390,000 (Direct Cost: ¥300,000、Indirect Cost: ¥90,000)
Fiscal Year 2022: ¥1,690,000 (Direct Cost: ¥1,300,000、Indirect Cost: ¥390,000)
Fiscal Year 2021: ¥2,470,000 (Direct Cost: ¥1,900,000、Indirect Cost: ¥570,000)
Keywords再生治療 / iPS細胞由来心筋細胞 / 細胞移植 / 冠動脈内投与 / カテーテル / 再生医療 / 直接注射
Outline of Research at the Start

近年,重症の心不全症例に対して,多能性幹細胞を由来とする心筋細胞の移植による心筋再生治療の有効性が示されているが,移植方法の違いによる有効性や安全性の評価の比較については十分行われておらず,最適な移植方法の開発が求められている。
そこで本研究では,心筋梗塞モデルのカニクイザルの心臓へ,直接注射法および冠動脈内投与法による心筋細胞移植を行い,移植方法の違いによるグラフトの生着や心機能改善効果,移植後不整脈の発生について検証する。

Outline of Final Research Achievements

We investigated the efficacy and safety of intracoronary administration and direct injection methods for transplanting human iPS cell-derived cardiomyocytes into the heart. Although intracoronary administration method confirmed graft survival in the host myocardium, it also caused large myocardial infarction and reduced cardiac function, which suggested that this method is inefficient for transplanting cardiomyocytes.
In a direct injection method, cell transplantation were conducted on cynomolgus monkeys with a myocardial infarction model, and the long-term survival of the grafts was confirmed in the cell transplant group, and an improvement in cardiac function was observed compared to the saline transplant group. In addition, it was revealed that the side effect of ventricular arrhythmia occurring after transplantation was significantly less than in previous reports.

Academic Significance and Societal Importance of the Research Achievements

本研究から,iPS細胞由来心筋細胞の移植法として,冠動脈内投与法は非効率的であると考えられたが,直接注射法は有効かつ安全な方法であることが示された。これらの知見は,iPS細胞由来心筋細胞移植の現実的なプロトコールの確立にもつながることが予想され,心筋再生治療のヒトへの臨床応用の実現化を大きく加速するものと考えられた。

Report

(4 results)
  • 2023 Annual Research Report   Final Research Report ( PDF )
  • 2022 Research-status Report
  • 2021 Research-status Report
  • Research Products

    (8 results)

All 2024 2023 2021 Other

All Journal Article (2 results) (of which Peer Reviewed: 2 results,  Open Access: 2 results) Presentation (2 results) (of which Int'l Joint Research: 1 results) Book (1 results) Remarks (3 results)

  • [Journal Article] Regeneration of Nonhuman Primate Hearts With Human Induced Pluripotent Stem Cell-Derived Cardiac Spheroids2024

    • Author(s)
      Kobayashi H, Tohyama S, Ichimura H, Ohashi N, Chino S, Soma Y, Tani H, Tanaka Y, Yang X, Shiba N, Kadota S, Haga K, Moriwaki T, Morita-Umei Y, Umei T, Sekine O, Kishino Y, Kanazawa H, Kawagishi H, Yamada M, Naritah K, Naito T, Seto T, Kuwahara K, Shiba Y, and Fukuda K
    • Journal Title

      Circulation

      Volume: 123 Issue: 8 Pages: 611-621

    • DOI

      10.1161/circulationaha.123.064876

    • Related Report
      2023 Annual Research Report
    • Peer Reviewed / Open Access
  • [Journal Article] Intracoronary transplantation of pluripotent stem cell-derived cardiomyocytes: Inefficient procedure for cardiac regeneration2023

    • Author(s)
      Kobayashi Hideki、Tohyama Shugo、Kanazawa Hideaki、Ichimura Hajime、Chino Shuji、Tanaka Yuki、Suzuki Yota、Zhao Jian、Shiba Naoko、Kadota Shin、Narita Kazumasa、Naito Takafumi、Seto Tatsuichiro、Kuwahara Koichiro、Shiba Yuji、Fukuda Keiichi
    • Journal Title

      Journal of Molecular and Cellular Cardiology

      Volume: 174 Pages: 77-87

    • DOI

      10.1016/j.yjmcc.2022.11.004

    • Related Report
      2023 Annual Research Report 2022 Research-status Report
    • Peer Reviewed / Open Access
  • [Presentation] Regeneration Of Primate Heart With Human IPSC-Derived Cardiac Spheroids2023

    • Author(s)
      Hideki Kobayashi
    • Organizer
      The 17th annual BCVS 2023 Scientific Sessions
    • Related Report
      2023 Annual Research Report
    • Int'l Joint Research
  • [Presentation] 冠動脈内投与法によるヒト多能性幹細胞由来心筋細胞移植の実現可能性について2021

    • Author(s)
      小林 秀樹
    • Organizer
      第262回日本循環器学会関東甲信越地方会
    • Related Report
      2021 Research-status Report
  • [Book] CURRENT THERAPY2024

    • Author(s)
      小林秀樹ほか
    • Total Pages
      88
    • Publisher
      株式会社ライフメディコム
    • ISBN
      4898133606
    • Related Report
      2023 Annual Research Report
  • [Remarks] ヒトiPS細胞から作製した心筋球移植による心臓再生に成功

    • URL

      https://www.shinshu-u.ac.jp/faculty/medicine/topics/2024/04/26186522.php

    • Related Report
      2023 Annual Research Report
  • [Remarks] 小林秀樹先生の心臓再生研究の成果が「Circulation」に掲載されました

    • URL

      https://shinshu-junkanki.jp/20240430-2/

    • Related Report
      2023 Annual Research Report
  • [Remarks] 小林先生の論文が採択

    • URL

      https://yshiba425.wixsite.com/regeneration/post/%E5%B0%8F%E6%9E%97%E5%85%88%E7%94%9F%E3%81%AE%E8%AB%96%E6%96%87%E3%81%8C%E6%8E%A1%E6%8A%9E

    • Related Report
      2023 Annual Research Report

URL: 

Published: 2021-04-28   Modified: 2025-01-30  

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