ACE2 overexpressing mesenchymal stem cells alleviates COVID-19 lung injury by inhibiting pyroptosis. Wei et al.
Description
Mesenchymal stem cells (MSCs) have shown some efficacy in the COVID-19 treatment. We proposed that exogenous supplementation of ACE2 via MSCs (ACE2-MSCs) might have better therapeutic effects. We constructed SARS-CoV-2 spike glycoprotein stably transfected AT-II and Beas-2B cells, and used SARS-CoV-2 spike pseudovirus to infect hACE2 transgenic mice. The results showed that 1) Spike glycoprotein of SARS-CoV-2-transfected AT-II and Beas-2B cells induced pyroptosis and apoptosis; 2) SARS-CoV-2 spike protein activates pyroptosis and the inflammatory response in both AT-II cells and Beas-2B cells and LPS treatment augments the responses; 3) The main factors of the inflammatory response and pyroptosis were downregulated in LPS-treated AT-II and Beas-2B cells by ACE2-MSCs application; 4) SARS-CoV-2 pseudovirus deteriorates mouse lung injury induced by LPS and increases the transcript expression levels of the main factors of cytokine storm and pyroptosis; 5) ACE2-MSCs alleviate SARS-CoV-2 pseudovirus-induced lung injury and inhibit the main factors mRNA of cytokine storm and pyroptosis. Moreover, compared to using MSCs or rh-ACE2 alone, the administration of ACE2-MSCs could much more significantly reduce these factors and alleviate lung injury in vivo and in vitro, which might be due to the increased activities of secretory ACE2. Our proposal is a promising therapeutic solution for preclinical or clinical research on COVID-19.