Mesenchymal stem cells (MSC) were suggested to be effective just after COVID-19 has raged around the world. For its mechanism of action, many groups have hypothesized that the anti-inflammatory effect of MSC suppresses cytokine storms, thereby acting effectively against COVID-19.
At our company, although we are aware that the anti-inflammatory effect is present, we conducted research since there may also be other mechanisms. The results showed that MSC and factors secreted from MSC have the effect of suppressing the gene expression of two infection mediators: ACE2, a protein present on the cell surface that acts as a receptor for SARS-CoV2, and TMPRSS2, a cell surface enzyme that increases the infection efficiency of SARS-CoV2.
As we further studied how MSC and their secretions suppress the gene expression of ACE2 and TMPRSS2, we found that they regulated the expression of both genes via a transcription factor called FOXO1. When cells were treated with AS1842856, an inhibitor of FOXO1 transcription factor, the gene expression of ACE2 and TMPRSS2 was suppressed in a dose-dependent manner. Furthermore, results suggesting the suppression of infection were obtained in a pseudo-viral infection model experiment. Currently, we are conducting joint research with other research institutions and are continuing further investigations.
In this manner, we aim to discover new drug seeds by deeply investigating how MSC and their secretions act on diseases and the corresponding mechanisms.
One of the issues with regenerative medicine is that “treatment costs are likely to be high.” We will investigate in detail the mechanism of “how MSC cure diseases” and discover new drug seeds, which will enable us to discover new inexpensive and effective drugs. Of course, some diseases can only be treated through the various functions of MSC. For such diseases, it would be better to use MSC and, at the same time, we keep searching new drugs.