Regeneration-associate cells-derived extracellular vesicles study

2021 Fiscal Year Final Research Report

• Project/Area Number: 20K17163
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53020:Cardiology-related
• Research Institution: Shonankamakura General Hospital (Center for Clinical and Translational Science)
• Principal Investigator: Salybekov Amankeldi 医療法人沖縄徳洲会湘南鎌倉総合病院(臨床研究センター), 一般再生医療研究部, 主任部長 (80850776)
• Project Period (FY): 2020-04-01 – 2022-03-31
• Keywords: 再生アソシエイト細胞 / 血管新生 / extracellular vesicles / miR / 細胞外小胞 / anti-fibrosis / cardiomyogenesis / exosomes

Outline of Final Research Achievements

In this study, we evaluated the therapeutic efficacy of RAC-derived extracellular vesicles (RACev) compared to mesenchymal stem cell-derived EVs (MSCev) in the context of myocardial infarction. In vitro, RACev markedly enhanced the viability, and proliferation of HUVECs in a dose-dependent manner than MSCev. Notably, systemic injection of RACev improved cardiac functions at 4 weeks, such as fractional shortening, and protection from mitral regurgitation than the MSCev. Histologically, the RACev showed less interstitial fibrosis and enhanced capillary densities compared to the MSCev group. These beneficial effects were coupled with significant expression of angiogenesis, anti-fibrosis, anti-inflammatory, and cardiomyogenesis-related miRs in RACev, while modestly in MSCev. Overall, repetitive systemic transplantation of RACev is superior to MSCev in terms of cardiac function enhancements via crucial angiogenesis, anti-fibrosis, anti-inflammation miR delivery to the ischemic tissue.

Free Research Field

Cardiovascular diseases (Cardiology)

Academic Significance and Societal Importance of the Research Achievements

学術的意義：RACevを確立し、in vitroおよびin vivoでその治療効果を評価した。本研究成果は、3つの国際学会および3つの査読付きジャーナルにて発表した。また、方法論、治療メカニズムなどについて国際出願済みである。
社会的意義：RACevは、同種異系移植で急性心虚血性疾患の治療効果が期待できることを示した。これは様々な病気を治療するために重要であり、大量生産を可能とするものである。