Development and application of a method for producing human cardiac tissue in pigs

2022 Fiscal Year Final Research Report

• Project/Area Number: 20H03768
• Research Category: Grant-in-Aid for Scientific Research (B)
• Allocation Type: Single-year Grants
• Section: 一般
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Keio University
• Principal Investigator: Tohyama Shugo 慶應義塾大学, 医学部(信濃町), 講師 (90528192)
• Co-Investigator(Kenkyū-buntansha): 中山 功一 佐賀大学, 医学部, 教授 (50420609)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: ヒトiPS細胞 / ブタ / バイオ３Dプリンタ / 心筋細胞 / 組織工学 / 免疫不全マウス

Outline of Final Research Achievements

Human iPSCs are expected to be applied to regenerative medicine and drug screening due to their capability of cardiac differentiation. However, human iPSC-derived cardiomyocytes have characteristics of fetal type, which directly leads to proarrhythmic effects in regenerative medicine and phenotypic variability in drug discovery research. On the other hand, various methods have been reported to promote cell maturation, including culture environment, tissue construction, and physical stimulation, but all of these methods are far from adult human myocardial tissue. In this study, we aim to develop a basic technology for the acceleration of the maturation in human iPSC-derived cardiac tissue by using pigs as in vivo reactors, to generate human iPSC-derived matured cardiac tissue, and to accelerate regenerative medicine and drug discovery research.

Free Research Field

再生医学

Academic Significance and Societal Importance of the Research Achievements

ヒトiPS細胞由来の未熟な心筋組織を成熟化させるためには、主に物理的刺激やECM、培養環境が重要であるとされているが、それらだけでは成熟な心筋組織を得るのに不十分である。一方で、ヒトiPS細胞由来心筋細胞を移植した際には、ヒトiPS細胞由来心筋細胞の成熟化が顕著に促進される。そこで、佐賀大が開発したバイオ３Dプリンタを用いた心筋チューブ組織構築を行い、ブタ等の大動物の血管に繋ぐことにより、血流だけでなく、生理的な動脈圧負荷をかけ、成熟化を促進することが可能である。ブタ生体内でヒト心筋組織を作製できれば、創薬や再生医療への応用が可能となる。