Tissue Repair Agent, Methods of Using Tissue Repair Agent, and Screening Methods

Overview

The problem that the present invention aims to solve is to provide a tissue repair agent capable of suppressing multiple cytokines involved in cytokine storms and repairing tissues damaged by cytokine storms. <SOD3 and Cytokine Storm Relationship> In the lungs of the elderly, SOD3 levels are low, suggesting an association with the exacerbation of COVID-19 due to cytokine storms. <New Insights in the Present Invention> The present inventors found that extracellular vesicles such as exosomes derived from the culture supernatant of specific mesenchymal stem cells contain abundant extracellular superoxide dismutase (SOD3) and exhibit high SOD activity. Furthermore, they discovered that these extracellular vesicles not only directly suppress inflammatory cytokines in cytokine storms induced by LPS administration but also exhibit a synergistic effect by promoting the repair of damaged tissues in the presence of cytokines such as IFNγ and TNFα. While the presence of SOD3 protein in exosomes has been known, it is the first time the present inventors have found that exosomes derived from the culture supernatant of specific mesenchymal stem cells exhibit very high SOD3 activity and contain more than an effective amount to repair tissues damaged by cytokine storms. Without this insight, it would not be conceivable to develop a tissue repair agent capable of suppressing cytokines involved in cytokine storms and repairing tissues damaged by cytokine storms, making the tissue repair agent of the present invention fundamentally different from conventional cytokine storm inhibitors. Furthermore, it is expected that elderly individuals with low SOD3 levels (Non-patent Document 6; ANTIOXIDANTS & REDOX SIGNALING (2020), 33, 2) may not be able to repair tissues solely by suppressing cytokines due to their low SOD3 levels. However, according to the present invention, it is possible to significantly repair tissues damaged by cytokine storms in elderly individuals.

As a result of diligent investigation to solve the above-mentioned problems, the present inventors have found that extracellular vesicles such as exosomes derived from the culture supernatant of specific mesenchymal stem cells contain extracellular superoxide dismutase (SOD3) and exhibit high SOD activity. Furthermore, the present inventors have found that the use of these extracellular vesicles can significantly suppress multiple cytokines involved in cytokine storms.