2023 Fiscal Year Final Research Report

Development of novel cell-free cardiac regenerative therapy using iPS cell-derived cardiac exosomes

Research Project

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Project/Area Number	21K19528
Research Category	Grant-in-Aid for Challenging Research (Exploratory)
Allocation Type	Multi-year Fund
Review Section	Medium-sized Section 55:Surgery of the organs maintaining homeostasis and related fields
Research Institution	National Cardiovascular Center Research Institute (2022-2023) Osaka University (2021)
Principal Investigator	Tominaga Yuji 国立研究開発法人国立循環器病研究センター, 病院, 医師 (80838558)
Co-Investigator(Kenkyū-buntansha)	河村拓史大阪大学, 大学院医学系研究科, 助教 (60839398)
Project Period (FY)	2021-07-09 – 2024-03-31
Keywords	iPS cell / iPS cardiomyocyte / Exosome / Extracellular vesicle / M2 macrophage / arteriogenesis / reduced fibrosis
Outline of Final Research Achievements	This study investigates extracellular vesicles (exosomes) secreted from stem cells, which are expected to be a foothold for the development of versatile cell-free myocardial regeneration therapy that does not require preparation and conditioning of transplanted cells. We are extracting extracellular vesicles from the culture medium obtained from our iPS cardiomyocyte large-scale culture system and examining their therapeutic effects. In 2021, we made significant strides by administering extracellular vesicles to rat models of myocardial infarction and analyzed their single-cell gene expression. We have conducted a detailed analysis of the mechanism of action of extracellular vesicles using the analysis results, and identify the mechanism based on in vitro, in vivo, and in silico data. The results of this study were published in 2023 by the Journal of Heart and Lung Transplantation.
Free Research Field	心臓血管外科、再生医療
Academic Significance and Societal Importance of the Research Achievements	本研究は、近年、移植細胞の準備・調整を要さない汎用性の高いcell-freeの心筋再生治療開発の足がかりとして期待されている、幹細胞などから分泌される細胞外小胞(exosome、extracellular vesicles)に関する研究である。我々が保有するiPS心筋細胞大量培養装置から得られた培地より、細胞外小胞を抽出し、その治療効果を検討を行なった。心筋梗塞モデルラットにおいて心機能改善、血管新生、線維化抑制を認めた。網羅的遺伝子発現解析の手法を用いて、そのメカニズムを解明した。今後の細胞外小胞の臨床応用へとつながる研究である。