ACE2 overexpressing mesenchymal stem cells alleviates COVID-19 lung injury by inhibiting pyroptosis

Jinhuan Wei; Rui Shang; Jiaqi Wang; Shengze Zhu; JianQiang Yin; Ying Chen; Yayu Zhao; Gang Chen

doi:10.1016/j.isci.2022.104046

ACE2 overexpressing mesenchymal stem cells alleviates COVID-19 lung injury by inhibiting pyroptosis

iScience. 2022 Apr 15;25(4):104046. doi: 10.1016/j.isci.2022.104046. Epub 2022 Mar 10.

Authors

Jinhuan Wei¹, Rui Shang², Jiaqi Wang¹, Shengze Zhu¹, JianQiang Yin³, Ying Chen², Yayu Zhao⁴, Gang Chen^{1

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Affiliations

¹ Center for Basic Medical Research, Medical School of Nantong University, Nantong, Jiangsu Province 226001, China.
² Department of Histology and Embryology, Medical School of Nantong University, Nantong, Jiangsu Province 226001, China.
³ Genesis Stem Cell Co. LTD, Nantong, Jiangsu Province 226009, China.
⁴ Key Laboratory of Neuroregeneration of Jiangsu and the Ministry of Education, Co-innovation Center of Neuroregeneration, Nantong University, Nantong, Jiangsu Province 226001, China.
⁵ Department of Anesthesiology, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province 226001, China.

Abstract

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.

Keywords: Biological sciences; Cell biology; Microbiology; Stem cells research.