Evaluation of autologous skeletal myoblast cell sheet on heart failure with congenital heart disease

2020 Fiscal Year Final Research Report

• Project/Area Number: 19K18177
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 55030:Cardiovascular surgery-related
• Research Institution: Osaka University
• Principal Investigator: Araki Kanta 大阪大学, 医学部附属病院, 医員 (90768144)
• Project Period (FY): 2019-04-01 – 2021-03-31
• Keywords: 先天性心疾患合併心不全 / 圧負荷右心不全 / 心筋再生療法 / 血管新生 / 自家骨格筋由来筋芽細胞シート

Outline of Final Research Achievements

Mini-pigs underwent pulmonary artery banding. Two months after banding, autologous skeletal myoblast sheets were placed on RV free wall. Groups were as follows: control (C), sheet implantation (S). Cardiac function analysis and C11-Acetate PET were performed before and two months after sheet implantation. Hearts were dissected for histologic and real-time PCR analysis.
Two months after sheet implantation, RV dysfunction was significantly ameliorated in group S than group C. PET revealed the deterioration of myocardial oxidative metabolism was suppressed in group S than group C. In histologic analysis, group S presented more angiogenesis in CD31 expression. In PCR analysis, mRNA expression of vascular endothelial growth factor was upregulated, and NOX2 was downregulated in group S than group C. Autologous skeletal myoblast sheet transplantation ameliorated metabolic and functional dysfunction in a porcine model of pressure-overloaded right heart by alleviation of MI.

Free Research Field

再生医療

Academic Significance and Societal Importance of the Research Achievements

圧負荷右心不全豚モデルにおいて、自家骨格筋由来筋芽細胞シートは右室心筋の虚血を改善し、右心不全の進行を抑制し得た本研究の結果により、自家骨格筋由来筋芽細胞シート治療が今後さらに増加する先天性心疾患を有する重症心不全患者の治療選択肢となりえる可能性が示唆された。