Anticoagulant and anti-fibrotic effects of mesenchymal stem cells overexpressing thrombomodulin

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K16220
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 53040:Nephrology-related
• Research Institution: Hiroshima University
• Principal Investigator: Ishiuchi Naoki 広島大学, 医系科学研究科(医), 共同研究講座講師 (30898010)
• Project Period (FY): 2022-04-01 – 2024-03-31
• Keywords: 間葉系幹細胞 / Thrombomodulin / アデノ随伴ウイルス / 血栓 / 腎線維化

Outline of Final Research Achievements

Adipose-derived mesenchymal stem cells (ASCs) exhibit anti-inflammatory and anti-fibrotic effects via their paracrine actions, and thereby are expected to be a new therapy to impede progression of renal fibrosis. Meanwhile, ASCs reportedly exhibit procoagulant activity compared to other mesenchymal stem cell types, raising concerns about thrombogenic risk in the clinical application. In this study, we found that ASCs overexpressing thrombomodulin (TM), anticoagulant and antifibrinolytic factor, dramatically reduce intravascular thrombus formations and rat death associated with thrombus formation induced by ASCs.TM-overexpressing ASCs can be safely used for cell therapy by reducing the risk of thromboembolism.

Free Research Field

腎臓内科学

Academic Significance and Societal Importance of the Research Achievements

本研究により、Thrombomodulinを過剰発現させた脂肪由来MSCは、血栓形成のリスクを大幅に減少させることが明らかとなった。この結果は、Thrombomodulinを高発現させた脂肪由来MSCが臨床研究で安全に使用できることを示唆しており、腎不全の進行を抑制するための有効な治療法になると考える。