Hypothesis for the management and treatment of the COVID-19-induced acute respiratory distress syndrome and lung injury using mesenchymal stem cell-derived exosomes

Abstract

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a member of the coronaviridae that causes respiratory disorders. After infection, large amounts of inflammatory cytokines are secreted, known as the cytokine storm. These cytokines can cause pulmonary damage induced by inflammation resulting in acute respiratory distress syndrome (ARDS), and even death. One of the therapeutic approaches for treatment of ARDS is a mesenchymal stem cell (MSC). MSCs suppress inflammation and reduce lung injury through their immunomodulatory properties. MSCs also have the potential to prevent apoptosis of the lung cells and regenerate them. But our suggestion is using MSCs-derived exosomes. Because these exosomes apply the same immunomodulatory and tissue repair effects of MSCs and they don't have problems associated to cell maintenance and injections. For investigation the hypothesis, MSCs should be isolated from tissues and characterized. Then, the exosomes should be isolated from the supernatants and characterized. These exosomes should be injected into a transgenic animal for COVID-19. In the final section, lung function assessment, histological examination, micro-CT, differential leukocyte, viral load analysis, cytokine assay, and CRP level analysis can be investigated. COVID-19 treatment is currently focused on supportive therapies and no vaccine has been developed for it. So, numerous researches are needed to find potential therapies. Since the pathogenesis of this disease was identified in previous studies and can cause lung injury with ARDS, investigation of the therapeutic approaches that can suppress inflammation, cytokine storm and ARDS can be helpful in finding a novel therapeutic approach for this disease.

Keywords: Acute respiratory distress syndrome; COVID-19; Exosomes; Mesenchymal stem cell; SARS-CoV-2.

Fig. 1

Immunopathogenesis of the SARS-CoV-2 and the therapeutic potential of the MSC exosomes. (A) SARS-CoV-2 infects type II alveolar epithelial cells or other target cells, which express ACE2. The influx of neutrophils, monocytes and T cells is induced by secretion of the chemokines. Accumulation of the inflammatory cells leads to the production of large amounts of pro-inflammatory cytokines, that is known as cytokine storm. Cytokine storm is the main cause of ARDS in COVID-19. These inflammatory responses may cause the apoptosis of the alveolar cells, lung fibrosis, edema, and organ failure. (B) MSCs and their exosomes suppress inflammation and reduce inflammation-induced lung injury through their immunomodulatory properties. These cells affect the macrophages and alter the phenotype of macrophages from M1 to M2 by releasing PG-E2. MSCs also reduce the production of the inflammatory cytokines and increase IL-10 production. IL-10 reduces neutrophils recruitment to the lungs. MSCs have also the tissue repair potential by producing KGF, VEGF, and HGF. These cells are involved in the pathogen clearance through expressing IDO.

Fig. 2

Testing the hypothesis. MSC, mesenchymal stem cell; SEM, scanning electron microscopy; TEM, transmission electron microscopy; DLS, dynamic light scattering. NTA, nanoparticle tracking analysis; ARDS, acute respiratory distress syndrome; BAL, bronchoalveolar lavage; CRP, C-reactive protein; ELISA, enzyme-linked immunosorbent assay.