About: Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2

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About: Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2 Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : covidontheweb.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2
Creator	Wang, Pengfei Xu, Dong Wang, Xing Schwartz, Robert Zhang, Zhao Lian, Qizhou Han, Yuling Ma, Ho, David Zhang, Tuo Tenoever, Benjamin Zhou, Xiaoya Chen, Huanhuan Chen, Shuibing Chen, Ya-Wen Chui, Yan Duan, Xiaohua Duan, Fuyu Evans, Todd Guo, Liyan Han, Teng Liao, Can Luo, Weiren Meyer, Edward Nilsson-Payant, Benjamin Thakur, Abhimanyu Xiang, Jenny Yang, Liuliu
Source	Medline; PMC
abstract	Dysfunctional immune responses contribute critically to the progression of Coronavirus Disease-2019 (COVID-19) from mild to severe stages including fatality, with pro-inflammatory macrophages as one of the main mediators of lung hyper-inflammation. Therefore, there is an urgent need to better understand the interactions among SARS-CoV-2 permissive cells, macrophage, and the SARS-CoV-2 virus, thereby offering important insights into new therapeutic strategies. Here, we used directed differentiation of human pluripotent stem cells (hPSCs) to establish a lung and macrophage co-culture system and model the host-pathogen interaction and immune response caused by SARS-CoV-2 infection. Among the hPSC-derived lung cells, alveolar type II and ciliated cells are the major cell populations expressing the viral receptor ACE2 and co-effector TMPRSS2, and both were highly permissive to viral infection. We found that alternatively polarized macrophages (M2) and classically polarized macrophages (M1) had similar inhibitory effects on SARS-CoV-2 infection. However, only M1 macrophages significantly up-regulated inflammatory factors including IL-6 and IL-18, inhibiting growth and enhancing apoptosis of lung cells. Inhibiting viral entry into target cells using an ACE2 blocking antibody enhanced the activity of M2 macrophages, resulting in nearly complete clearance of virus and protection of lung cells. These results suggest a potential therapeutic strategy, in that by blocking viral entrance to target cells while boosting anti-inflammatory action of macrophages at an early stage of infection, M2 macrophages can eliminate SARS-CoV-2, while sparing lung cells and suppressing the dysfunctional hyper-inflammatory response mediated by M1 macrophages.
has issue date	2020-08-20(xsd:dateTime)
bibo:doi	10.21203/rs.3.rs-62758/v1
bibo:pmid	32839764
has license	cc-by
sha1sum (hex)	e1c8ebe41c95aefbf9a2c8bbe2df4903075f5e23
schema:url	https://doi.org/10.21203/rs.3.rs-62758/v1
resource representing a document's title	Modeling COVID-19 with Human Pluripotent Stem Cell-Derived Cells Reveals Synergistic Effects of Anti-inflammatory Macrophages with ACE2 Inhibition Against SARS-CoV-2
has PubMed Central identifier	PMC7444287
has PubMed identifier	32839764
schema:publication	Res Sq
resource representing a document's body	covid:e1c8ebe41c95aefbf9a2c8bbe2df4903075f5e23#body_text
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