The mechanisms of antifibrotic effects of extracellular vesicles derived from human mesenchymal stem cells

2023 Fiscal Year Final Research Report

• Project/Area Number: 21K16122
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53030:Respiratory medicine-related
• Research Institution: Juntendo University
• Principal Investigator: Kadoya Kotaro 順天堂大学, 医学部, 非常勤助教 (10849706)
• Project Period (FY): 2021-04-01 – 2024-03-31
• Keywords: Extracellular vesicles / 間葉系幹細胞 / 肺線維芽細胞 / TGF-β / micro RNA

Outline of Final Research Achievements

When lung fibroblasts were subjected to TGFβ stimulation and treated with extracellular vesicle (EV) preparations derived from mesenchymal stem cells (MSCs), there was a notable inhibition of their migratory capabilities in response to fibronectin concentration gradients and a reduction in their ability to contract collagen gels. Additionally, these preparations suppressed the production of α-smooth muscle actin (αSMA) and type I collagen. Further investigations, including comprehensive miRNA analyses and miRNA mimic experiments of the MSC-derived EVs, identified a specific miRNA that exhibited anti-fibrotic effects. To explore the underlying mechanisms, the study focused on intracellular signaling pathways in the treated fibroblasts. It was demonstrated that the EV treatment suppressed fibrosis-related phosphorylation signaling and specific protein expression in lung fibroblasts, suggesting a potential therapeutic pathway for fibrotic diseases.

Free Research Field

肺線維症

Academic Significance and Societal Importance of the Research Achievements

本研究は、従来にない間葉系幹細胞由来Extracellular Vesicle (EV)による肺線維症の病態制御機序の解明を行い、間葉系幹細胞由来EVのタンパク質やmiRNAの新たな抗線維化標的因子の同定を行う。革新的な新規バイオ抗線維化薬剤として間葉系幹細胞由来EVの臨床応用に向けた基盤研究である。