期刊
ISCIENCE
卷 25, 期 4, 页码 -出版社
CELL PRESS
DOI: 10.1016/j.isci.2022.104046
关键词
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资金
- Key Research and Development Program (Social Development) of Jiangsu Province [BE2020667]
- National Natural Science Foundation of China [31872773, 32070998]
- National Key Research and Development Program of China [2017YFA0104704]
- Foundation of Jiangsu Province 333 Project High-level Talents [BRA2020076]
- Nantong Science and Technology Bureau [MS12020056]
- Postgraduate Research & Practice Innovation Program of Jiangsu Province [KYCX21_3097]
- Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD)
This study investigated the use of ACE2-MSCs for COVID-19 treatment. The results showed that ACE2-MSCs were more effective in reducing inflammatory factors and pyroptosis factors compared to using MSCs or rh-ACE2 alone, and they alleviated lung injury.
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 the release of apoptotic bodies and formation of membrane pores 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 significantly reduce these factors better and alleviate lung injury in vivo and in vitro, which might be because of the increased activities of secretory ACE2. Our proposal is a promising therapeutic solution for preclinical or clinical research.
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