Cardiac Regenerative therapy targeting on heart failure using synthetic nanoparticle including induced pluripotent stem cell derived cardiomyocytes exosomes.

使用合成纳米颗粒（包括诱导多能干细胞衍生的心肌细胞外泌体）针对心力衰竭的心脏再生疗法。

• 批准号: 21K16496
• 负责人: 樫山 紀幸
• 金额: $ 3万
• 依托单位: Osaka University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Early-Career Scientists
• 财政年份: 2021
• 资助国家: 日本
• 起止时间: 2021-04-01 至 2022-03-31
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-21K16496/
• 关键词: exosome; iPS心筋細胞; iPS細胞由来心筋; エクソソーム; 合成ナノパーティクル; 血管新生; 心不全

iPS心筋細胞由来exosomeの機能解析において、in vitro、in vivoにおいて作用メカニズムの詳細な解析を行なった。in vitroにおいては、exosome投与により心筋細胞のcontraction velocityの亢進を認め、また、血管内皮細胞におけるmigration能の亢進、fibroblastの活性化の抑制を認めた。各々の培養細胞のRNA sequenceを行うことによってmRNAの発現変動とともに、重要なmicroRNAの候補をpick upした。in vivoにおいては、rat心筋梗塞モデルに投与し、心機能の改善、生存率の改善を認めた。また、心筋組織のRNA sequenceを時系列で行うことで、心機能の改善に関与しているとも割れるサイトカインの発現変動と、重要と思われるmiRNAを認め、mechanismの解明を進めている。また、投与経路／投与方法の検討として、経静脈投与方法の確立を行なった。particle製剤と、exosome単体での血行動態、組織分布を比較するため、exosome単体での組織分布の検討を行い、histologyの解析を進めている。次年度は、exosome内包particle製剤を用いた、投与後の組織分布、drug delivery効率、治療効果の検討を行う。

The origin of iPS heart disease cell exosome machine can be used to analyze the effects of different drugs, such as in vitro, in vivo, etc. The expression of in vitro, exosome, contraction velocity and vascular endothelial cell migration were increased, while the activation of fibroblast was suppressed. In each RNA sequence program, there will be a lot of activity in the mRNA program, as well as an important microRNA waiting list for the pick up program. In vivo myocardial infarction, rat myocardial infarction, cardiac function improvement, survival rate improvement were recognized. The organization of the heart, the organization of the RNA sequence and the organization of the heart can improve the performance of the system and improve the performance of the system. You can realize the movement of the system, the important ideas of the miRNA, and the information of the mechanism. Investment, investment and method, investment and method, investment and method. Particle profile, exosome profile, tissue distribution, exosome profile, and histology analysis were analyzed. In the next year, exosome included the use of particle drugs, tissue distribution of investment and post-treatment, drug delivery infection rate, and treatment results.

项目成果

Mechanism of Cardiac Repair in Rat Myocardial Infarction Model Treated with Extracellular Vesicles from Differentiating Induced Pluripotent Stem Cell-Derived Cardiomyocytes

分化诱导多能干细胞来源的心肌细胞外囊泡治疗大鼠心肌梗死模型的心脏修复机制

• 发表时间: 2021
• 作者: Yuji Tominaga;S Miyagawa;Noriyuki Kashiyama;Yoshiki Sawa;et al.
• 通讯作者: et al.