Overexpression of Thrombomodulin in Adipose-Derived Mesenchymal Stem Cells Reduces Thrombogenic Risk and Enhances Therapeutic Efficacy.

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

• Level A · Stronger Clinical Evidence
• Level B · Emerging clinical evidence with positive signals
• Level C · Early human research exploring benefits
• Level D · Scientific groundwork from lab and animal studies
• Emerging · Emerging topic under active research

Abstract (original English)

Thrombomodulin on the cell surface acts as an anticoagulant and antifibrinolytic factor by binding to thrombin. Enhancement of thrombomodulin expression reduced renal infarction and pulmonary embolism induced by adipose-derived mesenchymal stem cells. Adipose-derived mesenchymal stem cells with enhanced thrombomodulin potentiated anti-inflammation and antifibrotic effects. Adipose-derived mesenchymal stem cells (ASCs) are expected to be a new therapy for organ injury; however, they were reported to have procoagulant activity, raising concerns about thrombogenic risk. Thrombomodulin acts as an anticoagulant factor by binding to thrombin, leading to the hypothesis that ASCs overexpressing thrombomodulin (TM-ASCs) could be safely used for cell therapy by reducing the risk of thromboembolism. TM-ASCs were generated using adeno-associated virus carrying thrombomodulin cDNA. To examine the risk of ASC-induced renal infarction, ASCs were administered through renal artery into rats with unilateral ischemia-reperfusion injury (IRI) and contralateral nephrectomy. To assess the risk of ASC-induced pulmonary embolism, ASCs were injected into rats through tail vein. In addition, we examined whether TM-ASCs potently inhibited inflammatory cell infiltration and kidney fibrosis in IRI rats. Furthermore, we explored synthetic compounds that enhanced thrombomodulin expression in ASCs. Overexpres

Evidence level

Evidence from laboratory and animal studies provides groundwork for understanding mechanisms and potential before human studies continue.

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