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Copyright ©The Author(s) 2020. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Stem Cells. Oct 26, 2020; 12(10): 1067-1079
Published online Oct 26, 2020. doi: 10.4252/wjsc.v12.i10.1067
Mesenchymal stem cells as living anti-inflammatory therapy for COVID-19 related acute respiratory distress syndrome
Feng Lin, Thomas E Ichim, Sandeep Pingle, Lawrence D Jones, Santosh Kesari, Shashaanka Ashili
Feng Lin, Thomas E Ichim, Sandeep Pingle, Lawrence D Jones, Shashaanka Ashili, Research and Development, CureScience, San Diego, CA 92121, United States
Santosh Kesari, Cancer Center, John Wayne Cancer Institute and Pacific Neuroscience Institute at Providence Saint John's Health Center, Santa Monica, CA 90404, United States
Author contributions: All authors contributed equally to this paper in conception, literature review and analysis, drafting, critical revision and editing, and approval of the final version.
Conflict-of-interest statement: No conflict of interest to report.
Open-Access: This article is an open-access article that was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution NonCommercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Corresponding author: Feng Lin, PhD, Research Scientist, Research and Development, CureScience, No. 10225 Barnes Canyon Road A207, San Diego, CA 92121, United States. flin@curescience.org
Received: July 6, 2020
Peer-review started: July 6, 2020
First decision: July 30, 2020
Revised: August 13, 2020
Accepted: September 14, 2020
Article in press: September 14, 2020
Published online: October 26, 2020
Processing time: 111 Days and 17.2 Hours
Abstract

Coronavirus disease 2019 (COVID-19), a pandemic disease caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV2), is growing at an exponential rate worldwide. Manifestations of this disease are heterogeneous; however, advanced cases often exhibit various acute respiratory distress syndrome-like symptoms, systemic inflammatory reactions, coagulopathy, and organ involvements. A common theme in advanced COVID-19 is unrestrained immune activation, classically referred to as a “cytokine storm”, as well as deficiencies in immune regulatory mechanisms such as T regulatory cells. While mesenchymal stem cells (MSCs) themselves are objects of cytokine regulation, they can secrete cytokines to modulate immune cells by inducing anti-inflammatory regulatory Treg cells, macrophages and neutrophils; and by reducing the activation of T and B cells, dendritic and nature killer cells. Consequently, they have therapeutic potential for treating severe cases of COVID-19. Here we discuss the unique ability of MSCs, to act as a “living anti-inflammatory”, which can “rebalance” the cytokine/immune responses to restore equilibrium. We also discuss current MSC trials and present different concepts for optimization of MSC therapy in patients with COVID-19 acute respiratory distress syndrome. 

Keywords: Mesenchymal stem cells; SARS-CoV-2; COVID-19; Cytokine storm; Acute respiratory distress syndrome; Immunomodulation

Core Tip: Coronavirus disease 2019 a disease caused by the severe acute respiratory syndrome coronavirus 2, is growing exponentially, with no treatments currently available. Preclinical and clinical studies have shown that mesenchymal stem cells (MSCs) work in reversing acute respiratory distress syndrome caused by other conditions such as influenza virus infection, or sepsis. In this review we discuss the unique ability of MSCs, to act as a “living anti-inflammatory”, which can “rebalance” the cytokine/immune responses to restore equilibrium.