Elucidating Mechanisms of Epicardial Cell Proliferation and Differentiation and Developing Technologies for Their Application

2023 Fiscal Year Final Research Report

• Project/Area Number: 21H02912
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Kyoto University
• Principal Investigator: Yoshida Yoshinori 京都大学, iPS細胞研究所, 准教授 (20447965)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: 心外膜細胞 / 心筋細胞 / iPS細胞 / CDH18 / オルガノイド

Outline of Final Research Achievements

This study focused on understanding the biology of epicardial cells, a crucial source of non-cardiac myocytes in the heart. We established a method for efficiently generating epicardial cells from induced pluripotent stem cells (iPSCs) and demonstrated that CDH18 is specifically expressed in these cells. Knockdown of CDH18 enhances their differentiation into smooth muscle cells, and inhibiting specific signaling pathways can further induce these cells to mature. Additionally, we developed a method to produce mature cardiac 3D tissues, such as organoids, using epicardial cells and cardiomyocytes derived from iPSCs. We confirmed that these cardiac organoids can be transplanted into an immunodeficient mouse model of myocardial infarction, offering a potential reconstructive treatment for damaged myocardial tissues.

Free Research Field

循環器内科学、幹細胞生物学

Academic Significance and Societal Importance of the Research Achievements

iPS細胞から作製したヒト立体心筋組織は再生医療や創薬研究において今後重要な役割を担うことが期待されているが、成人の心筋組織に近いような心筋組織の作製法については確立されていない。その理由として、心筋組織において大きな割合を占める非心筋細胞についての理解が進んでいないことが挙げられる。心外膜細胞は心臓の臓器形成において非心筋細胞の主要なソースとなる細胞である。本研究は心外膜細胞のバイオロジーを理解し、iPS細胞から作製した心外膜細胞の制御法を確立し、立体心筋組織の作製法の確立を目指す研究であり、心筋組織を用いた再生医療や創薬研究の発展に寄与することが期待される。