Mesenchymal stem cell immunomodulation: In pursuit of controlling COVID-19 related cytokine storm

Abstract

The coronavirus disease 2019 (COVID-19) pandemic has grown to be a global public health crisis with no safe and effective treatments available yet. Recent findings suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the coronavirus pathogen that causes COVID-19, could elicit a cytokine storm that drives edema, dysfunction of the airway exchange, and acute respiratory distress syndrome in the lung, followed by acute cardiac injury and thromboembolic events leading to multiorgan failure and death. Mesenchymal stem cells (MSCs), owing to their powerful immunomodulatory abilities, have the potential to attenuate the cytokine storm and have therefore been proposed as a potential therapeutic approach for which several clinical trials are underway. Given that intravenous infusion of MSCs results in a significant trapping in the lung, MSC therapy could directly mitigate inflammation, protect alveolar epithelial cells, and reverse lung dysfunction by normalizing the pulmonary microenvironment and preventing pulmonary fibrosis. In this review, we present an overview and perspectives of the SARS-CoV-2 induced inflammatory dysfunction and the potential of MSC immunomodulation for the prevention and treatment of COVID-19 related pulmonary disease.

Co-Administration of Menstrual Blood-Derived Stem Cells and Remdesivir for the Treatment of Severe Coronavirus Disease 2019 (COVID-19) Induced Pneumonia: A Research Protocol

“…It is expected that the treatment group will have a shorter time of recovery than the control group. Given MSCs' immunomodulatory properties [19,32], it is expected that the treatment group will show a greater reduction in pro-inflammatory cytokine (including IL-1β, IL-2, IL-6, TNF-α, IFN-γ) concentrations and a greater increase in anti-inflammatory cytokine (including IL-4, IL-10) concentrations [43], as compared to the control group. For the combination therapy to be considered efficacious, either the time of recovery must be significantly different between treatment and control groups, or the changes in concentrations of all co-primary cytokine endpoints must be significantly different between treatment and control groups.…”

SARS-CoV-2 Infection and Lung Regeneration

“…MSC-derived secretomes contain soluble factors (chemokines, growth factors, etc.) and extracellular vesicles that may control cytokine storm, reduce apoptosis of alveolar epithelial cells and endothelial cells, and promote angiogenesis and alveolar epithelial regeneration in COVID-19 patients ( 210 – 212 ). MSC or MSC exosomes also reduced fibroblast activation and ECM deposition ( 213 – 216 ).…”

Role of PD-L1 in licensing immunoregulatory function of dental pulp mesenchymal stem cells

“…As previously demonstrated, DPSCs are able to trigger lymphocytes apoptosis by activating the Fas/FasL pathway [ 12 – 14 ]. Moreover, DPSCs exert immunomodulatory properties even through the modulation of pro-inflammatory cytokines release when exposed to activated peripheral blood mononuclear cells (PBMCs) obtained from COVID-19 patients [ 15 , 16 ]. To this regard, the immunomodulatory/anti-inflammatory ability of DPSCs can be induced by the inflammatory microenvironment itself shaping a plastic immunosuppressive potential [ 17 , 18 ].…”