Development of heart failure treatment with micro-cardiac tissues with vascular network

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09507
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Cardiovascular medicine
• Research Institution: Keio University
• Principal Investigator: Fujita Jun 慶應義塾大学, 医学部(信濃町), 特任准教授 (10306706)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: 心不全 / 多能性幹細胞 / 心筋細胞 / 微小心筋組織 / 血管構築 / iPS細胞 / ES細胞 / 再生医療

Outline of Final Research Achievements

The optimal conditions for preparation of micro-cardiac tissues (MCT) were determined. Their maturity and the importance of the oxygen supply were confirmed. We established a massive two-dimensional culture method of human iPS cell-derived cardiomyocytes to obtain high-quality cardiomyocytes. MCT were transplanted to hearts of immunodeficient mice. The transplanted MCT were engrafted in large quantities even in the long term after transplantation, and vascular network was confirmed. MCT was transplanted to myocardial infarction models in immunodeficient rats, as well. A large number of transplanted MCT were engrafted, and their cardiac function significantly improved even in the long term after transplantation. The engrafted MCT expressed connexin 43 and did not induce any lethal arrhythmia. From these results, it has become clear that MCT based on high-quality human cardiomyocytes has vascular network, and safely and efficiently improves cardiac function in heart failure.

Free Research Field

循環器内科

Academic Significance and Societal Importance of the Research Achievements

ヒトES細胞、iPS細胞由来の再生心筋細胞を用いた心不全治療は、ドナー不足で移植数が伸び悩む心臓移植の代替療法として期待されている。しかし、細胞治療の成功は移植細胞がレシピエントの心臓に長期間生着できるかどうかにかかっている。本研究成果より高品質な心筋細胞を基盤として構築された微小心筋組織は血管網を有し、レシピエントの血流から酸素と栄養が供給されることによって長期生着することが明らかになった。さらに、有意な致死性不整脈を惹起せずに心機能を改善することが確認された。この方法により、再生心筋細胞を用いた重症心不全治療の革新的成果が期待できることより学術的および社会的意義は極めて大きい。