2. Academic Validation
  3. Engineering mesenchymal stromal cells with neutralizing and anti-inflammatory capability against SARS-CoV-2 infection

Engineering mesenchymal stromal cells with neutralizing and anti-inflammatory capability against SARS-CoV-2 infection

  • Mol Ther Methods Clin Dev. 2021 Jun 11;21:754-764. doi: 10.1016/j.omtm.2021.05.004.
Xiaoqing Zhang 1 2,  Ping Han 1 2,  Haiyong Wang 1 2,  Yanqin Xu 1 2,  Fanlin Li 1 2,  Min Li 1 2,  Lilv Fan 1 2,  Huihui Zhang 1 2,  Qiang Dai 1 2,  Hao Lin 1 2,  Xinyue Qi 1 2,  Jie Liang 1 2,  Xin Wang 3,  Xuanming Yang 1 2
Affiliations

Affiliations

  • 1 Sheng Yushou Center of Cell Biology and Immunology, School of Life Sciences and Biotechnology, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 2 Joint International Research Laboratory of Metabolic & Developmental Sciences, Shanghai Jiao Tong University, Shanghai 200240, China.
  • 3 Shanghai Longyao Biotechnology Limited, Shanghai 201203, China.
PMID: 34007862 DOI: 10.1016/j.omtm.2021.05.004
Abstract

The emergence of the novel human severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has led to the pandemic of coronavirus disease 2019 (COVID-19), which has markedly affected global health and the economy. Both uncontrolled viral replication and a proinflammatory cytokine storm can cause severe tissue damage in patients with COVID-19. SARS-CoV-2 utilizes angiotensin-converting Enzyme 2 (ACE2) as its entry receptor. In this study, we generated ACE2 extracellular domain-Fc and single-chain variable fragment-interleukin 6 (IL-6) single-chain variable fragment against IL-6 receptor (scFv-IL6R)-Fc fusion proteins to differentially neutralize viruses and ameliorate the cytokine storm. The human ACE2 (hACE2)1-740-Fc fusion protein showed a potent inhibitory effect on pseudo-typed SARS-CoV-2 entry and a good safety profile in mice. In addition, scFv-IL6R-Fc strongly blocked IL-6 signal activation. We also established a mesenchymal stromal cell (MSC)-based hACE21-740-Fc and scFv-IL6R-Fc delivery system, which could serve as a potential therapy strategy for urgent clinical needs of patients with COVID-19.

Keywords

ACE2; COVID-19; IL-6 blockade; SARS-CoV-2; cell therapy; mesenchymal stromal cell.

Figures
Products
  • Cat. No.
    Product Name
    Description
    Target
    Research Area
  • HY-D0938
    99.01%, Cell Proliferation Fluorescent Probe