Creation of cardiac organoids and bio-artificial hearts using self-organization ability through sympathetic nerve crosstalk

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H03808
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 90110:Biomedical engineering-related
• Research Institution: Osaka University
• Principal Investigator: LEE JONG-KOOK 大阪大学, 大学院医学系研究科, 特任教授(常勤) (60303608)
• Co-Investigator(Kenkyū-buntansha): 坂田 泰史 大阪大学, 大学院医学系研究科, 教授 (00397671)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 三次元心筋組織構築 / 交感神経 / 臓器間クロストーク / iPS細胞

Outline of Final Research Achievements

In the recellularized 3D cardiac tissue, pharmacological responses to cardiotonic agents comparable to those in vivo were observed. The presence of rat sympathetic nerve cells promoted the self-organization and maturation of human iPS-derived cardiomyocytes, as reconfirmed in an in vitro system. We investigated the relationship between stress fibers (actin) and YAP signaling, related to cell proliferation and migration, in human iPS-derived cardiomyocytes and reported our findings. We established techniques for evaluating the functional characteristics of human iPS-derived atrial and ventricular myocytes, developed foundational technologies for a drug discovery platform, and reported these findings. In the co-culture system of human iPS cardiomyocytes and sympathetic nerves, the increase in spontaneous beating rate after nicotine addition was more pronounced.

Free Research Field

再生医学、組織工学、心臓電気生理学

Academic Significance and Societal Importance of the Research Achievements

本課題においては、研究代表者らが見出した「交感神経との共培養がiPS 心筋の自己組織化と成熟化を促進する」現象を再確認し、iPS心筋を用いた三次元心筋組織の構築と機能・形態評価を行い、「臓器間クロストーク」の影響を調べた。
本研究は、生体模倣系に基づく創薬プラットフォームを含む社会実装に向けたアプローチに有用な知見をもたらした。1.創薬・再生治療に利用可能な三次元心筋組織を構築するためには、臓器間クロストーク（交感神経-心筋）による心筋の自己組織化と成熟性促進が有用であることを明らかにした。2.交感神経支配を有する三次元心筋組織を構築した。