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Review
. 2020 Sep;21(3):405-425.
doi: 10.1007/s10561-020-09842-3. Epub 2020 Jun 25.

Auxiliary role of mesenchymal stem cells as regenerative medicine soldiers to attenuate inflammatory processes of severe acute respiratory infections caused by COVID-19

Peyvand Parhizkar Roudsari  1 , Sepideh Alavi-Moghadam  2 , Moloud Payab  3 , Forough Azam Sayahpour  4 , Hamid Reza Aghayan  2 , Parisa Goodarzi  5 , Fereshteh Mohamadi-Jahani  5 , Bagher Larijani  6 , Babak Arjmand  7   8
Affiliations
Review

Auxiliary role of mesenchymal stem cells as regenerative medicine soldiers to attenuate inflammatory processes of severe acute respiratory infections caused by COVID-19

Peyvand Parhizkar Roudsari et al. Cell Tissue Bank. 2020 Sep.

Abstract

Acute respiratory infections as one of the most common problems of healthcare systems also can be considered as an important reason for worldwide morbidity and mortality from infectious diseases. Coronaviruses are a group of well-known respiratory viruses that can cause acute respiratory infections. At the current state, the 2019 novel coronavirus is cited as the most worldwide problematic agent for the respiratory system. According to investigations, people with old age and underlying diseases are at higher risk of 2019 novel coronavirus infection. Indeed, they may show a severe form of the disease (with severe acute respiratory infections). Based on the promising role of cell therapy and regenerative medicine approaches in the treatment of several life-threatening diseases, it seems that applying cell-based approaches can also be a hopeful strategy for improving subjects with severe acute respiratory infections caused by the 2019 novel coronavirus. Herein, due to the amazing effects of mesenchymal stem cells in the treatment of various diseases, this review focuses on the auxiliary role of mesenchymal stem cells to reduce inflammatory processes of acute respiratory infections caused by the 2019 novel coronavirus.

Keywords: ARDS; COVID-19; Cell therapy; Coronavirus; Mesenchymal stem cells; Pneumonia; Regenerative medicine.

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Conflict of interest statement

There is no conflict of interest.

Figures

Fig. 1
Fig. 1
Acute Respiratory Distress Syndrome (ARDS). Pulmonary or non-pulmonary infection, severe sepsis, aspiration of gastric contents, hemorrhage and shock are mentioned to be some of the causes for ARDS. Pathological findings of ARDS in lungs can be divided into three groups depending on the phase of occurrence; in the acute phase, interstitial and alveolar edema, accumulation of neutrophils, macrophages and red blood cells in the alveoli, endothelial and epithelial injury; in the subacute phase, reabsorption of edema, signs of repairing, infiltration of fibroblasts, collagen deposition and in chronic phase, more mononuclear cells, more fibrosis, and epithelial repairing and also the signs of resolution of the acute neutrophilic infiltration are the characteristics of findings in lungs (Matthay and Zemans 2011)
Fig. 2
Fig. 2
Nidovirales Order. Nidovirales order contains three families: Arteriviridae, Roniviridae and Coronaviridae. Torovirinae and Coronavirinae are subfamilies of Coronaviridae and Coronavirinae includes four genera: Alphacoronaviruses, Betacoronaviruses, Gammacoronaviruses and Deltacoronaviruses (Fehr and Perlman 2015), which are subdivided into more subgenera (Lin et al. 2019). SARSr-CoV, MERSr-CoV and SARS-CoV-2 are three species of Betacoronaviruses genera (Guo et al. 2020)
Fig. 3
Fig. 3
Inflammatory Process of Acute Respiratory Infections Caused by COVID-19. Coronavirus particles containing spike (S), membrane (M), envelope (E) and nucleocapsid (N) are CoVs main structural proteins (Fehr and Perlman 2015). Aerosolized uptake of SARS-CoV-2, infection of Angiotensin-converting enzyme 2 (ACE2) expressing target cells such as alveolar type2 cells, delayed or suppressed Type I interferon (IFN) responses, viral replication, the influx of neutrophils and monocytes/macrophages, activation of T helper1/17 (Th1/Th17) associated with exacerbation of inflammatory responses, production of specific antibodies from B-cells/plasma cells and hyperproduction of pro-inflammatory cytokines called “cytokine storms”(which leads to the immunopathology of lung) are the major viral-host Interactions (Prompetchara et al. 2020). The cytokine storm might lead to acute respiratory distress syndrome (ARDS), multiple organ failure (MOF) and eventually death in severe cases of COVID-19 (Cheng et al. 2020)
Fig. 4
Fig. 4
Effects of mesenchymal stem cells on lung in acute respiratory infections caused by COVID-19 based on cell-to-cell communication and releasing immunomodulatory molecules. Mesenchymal stem cells (MSCs) can release prostaglandin E2(PGE2) to provoke the generation of anti-inflammatory cytokines from macrophages and inhibiting ongoing T cell-dependent inflammation, transforming growth factor-beta (TGF-β), nitric oxide (NO), and indoleamine 2,3-dioxygenase (IDO) to suppress ongoing T cell-dependent inflammation, support the macrophages differentiation into the M2 phenotype for providing anti-inflammatory cytokines, suppress neutrophil intravasation and pro-inflammatory activation by TGF-β. Promote proliferation of epithelial cells and induce protection of vascular permeability by releasing keratinocyte growth factor (KGF), vascular endothelial growth factor (VEGF), and hepatocyte growth factor (HGF) (Wang et al. ; Harrell et al. , , ; Caretti et al. 2020)
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