Tissue Repair Agent, Method of Using Tissue Repair Agent, and Screening Metho

Summary

The problem that the present invention seeks to solve is to provide a tissue repair agent capable of inhibiting multiple cytokines involved in a cytokine storm and repairing tissues damaged by a cytokine storm.

<The Relationship Between SOD3 and Cytokine Storm>

In the lungs of elderly individuals, there is a reduced presence of SOD3, and this has been suggested to be associated with the severity of COVID-19, which is believed to originate from cytokine storms.

<New Findings in the Present Invention>

The present inventors have discovered that microvesicles, such as exosomes, derived from the culture supernatant of specific mesenchymal stem cells contain a large amount of extracellular superoxide dismutase 3 (SOD3) and exhibit high SOD activity. Furthermore, it has been found that these microvesicles not only directly suppress inflammatory cytokines in the cytokine storm induced by LPS administration but also have a synergistic effect, as SOD3 contained in these microvesicles promotes the repair of damaged tissues in the presence of cytokines, particularly IFNγ and TNFα.

Until now, the presence of SOD3 protein in exosomes has been known. However, the inventors of the present invention were the first to discover that exosomes derived from the culture supernatant of specific mesenchymal stem cells exhibit exceptionally high SOD3 activity and contain an effective amount exceeding what is necessary to repair tissues damaged by cytokine storms. Without this discovery, it would not have been possible to conceive a tissue repair agent that can suppress cytokines involved in cytokine storms and repair tissues damaged by cytokine storms. Therefore, the tissue repair agent of the present invention operates on a completely different mechanism from conventional cytokine storm inhibitors.

Furthermore, in elderly individuals with reduced SOD3 levels (Non-patent literature 6; ANTIOXIDANTS & REDOX SIGNALING (2020), 33, 2), it is anticipated that tissue repair may not occur solely by suppressing cytokines due to the low levels of SOD3. However, according to the present invention, significant tissue repair in elderly individuals with cytokine storm-induced tissue damage can be achieved.

As a result of intensive investigation to address the above-mentioned issue, the inventors of the present invention have discovered that microvesicles, 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 microvesicles can significantly suppress multiple cytokines associated with cytokine storms.