Mesenchymal Stromal Cells: Potential Option for COVID-19 Treatment

Abstract

The COVID-19 pandemic has significantly impacted the way of life worldwide and continues to bring high mortality rates to at-risk groups. Patients who develop severe COVID-19 pneumonia, often complicated with ARDS, are left with limited treatment options with no targeted therapy currently available. One of the features of COVID-19 is an overaggressive immune reaction that leads to multiorgan failure. Mesenchymal stromal cell (MSC) treatment has been in development for various clinical indications for over a decade, with a safe side effect profile and promising results in preclinical and clinical trials. Therefore, the use of MSCs in COVID-19-induced respiratory failure and ARDS was a logical step in order to find a potential treatment option for the most severe patients. In this review, the main characteristics of MSCs, their proposed mechanism of action in COVID-19 treatment and the effect of this therapy in published case reports and clinical trials are discussed.

Keywords: ARDS; COVID-19; MSCs; immunomodulation; mesenchymal stromal cells.

Figure 1

Presumed effect of COVID-19 mesenchymal stem cell therapy. Intravenous administration enables MSCs to travel to the lung microvasculature. MSCs extravasate in the alveoli and are then found in the proinflammatory microenvironment caused by the replication of the virus and subsequent immune response, causing the “cytokine storm”. MSCs are stimulated by the surrounding cytokines and respond by secreting molecules that suppress inflammation, have an antimicrobial effect, cause lymphocyte chemotaxis, stimulate macrophages to change their phenotype from proinflammatory M1 phenotype to anti-inflammatory M2 phenotype. They also inhibit T-cell proliferation and induce T-cell apoptosis and differentiation into T-regulatory cells. MSC–mesenchymal stem cell, PGE2–prostaglandin E2, TGF-β1–transforming growth factor β1, HGF–hepatocyte growth factor, SDF-1–stromal cell-derived factor 1, NO–nitrous oxide, IDO–indoleamine 2,3-dioxygenase, IL–interleukin, IL-1Ra–IL-1 receptor antagonist, sTNFR–soluble tumor necrosis factor α receptor, CXCR3–C-X-C motif chemokine receptor 3, CCR5–C-C motif chemokine receptor 5, ICAM-1–intracellular adhesion molecule 1, VCAM-1–vascular cell adhesion protein 1, LL-37–human cathelicidin antimicrobial peptide, HBD–human beta defensin, NK–natural killer, T-cell–T lymphocyte, T-reg–regulatory T lymphocyte. Created with BioRender.com.