iScience | VOL. 25
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Poly(I:C) enhances mesenchymal stem cell control of myeloid cells from COVID-19 patients.

Publication Date May 20, 2022

Abstract

Mesenchymal stem cells (MSCs) are being studied for the treatment of COVID-19-associated critical illness, due to their immunomodulatory properties. Here, we hypothesized that viral mimic-priming improves MSCs' abilities to rebalance the dysregulated immune responses in COVID-19. Transcriptome analysis of poly(I:C)-primed MSCs (pIC-MSCs) showed upregulation of pathways in antiviral and immunomodulatory responses. Together with increased expression of antiviral proteins such as MX1, IFITM3, and OAS1, these changes translated to greater effector functions in regulating monocytes and granulocytes while further enhancing MSCs' ability to block SARS-CoV-2 pseudovirus entry into epithelial cells. Most importantly, the addition of pIC-MSCs to COVID-19 patient whole blood significantly reduced inflammatory neutrophils and increased M2 monocytes while enhancing their phagocytic effector function. We reveal for the first time that MSCs can be primed by Toll-like receptor 3 agonist to improve their ability to rebalance the dysregulated immune responses seen in severe SARS-CoV-2 infection.

Concepts
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Mesenchymal Stem Cells
M2 Monocytes
Pseudovirus Entry
Immunomodulatory Responses
Toll-like Receptor
Immunomodulatory Properties
COVID-19 Patient
Effector Function
Epithelial Cells
Critical Illness

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