Long COVID-19 is a public health concern globally. Recent clinical data suggest that COVID-19 can cause various complications that last weeks to months after initial recovery. SARS-CoV-2 are well known to infect many organs, not only lung tissue but also cardiomyocytes, intestine, and central nervous system. Thus, establishment of appropriate animal and in vitro models for COVID-19 is critical to elucidate pathological mechanisms and drug development.
We have made various organ models from human iPS cells and evaluated their usefulness as SARS-CoV-2 infection models. We found that SARS-CoV-2 infected human iPSC-derived cardiomyocytes efficiently. Imaging analysis revealed that SARS-CoV-2 induced contractile dysfunction in iPSC-cardiomyocytes. Next-generation sequencing analysis revealed that SARS-CoV-2 reduced the expression of proteins related to contractility, suggesting that SARS-CoV-2 directly infects the cardiomyocytes and induces dysfunction. These observations are consistent with the clinical observations. In addition to cardiomyocytes, we found that SARS-CoV-2 also infected into iPSC-based brain blood barrier, and small intestinal epithelial cells.
In the symposium, we would like to talk about the iPSC-based models of SARS-CoV-2 infection and discuss the advantages and drawbacks.