First Author | Wei J | Year | 2022 |
Journal | iScience | Volume | 25 |
Issue | 4 | Pages | 104046 |
PubMed ID | 35287354 | Mgi Jnum | J:336028 |
Mgi Id | MGI:7256178 | Doi | 10.1016/j.isci.2022.104046 |
Citation | Wei J, et al. (2022) ACE2 overexpressing mesenchymal stem cells alleviates COVID-19 lung injury by inhibiting pyroptosis. iScience :104046 |
abstractText | 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 spike glycoprotein transfection triggers apoptotic bodies's release and membrane pores's formation in pyroptosis. Inflammatory factors and pyroptosis factors were highly upregulated by spike glycoprotein transfection. SARS-CoV-2 spike pseudovirus worsened lung injury and increased the main factors of cytokine storm and pyroptosis. 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. |