Review
Mesenchymal stromal/stem cells (MSCs) and MSC-derived extracellular vesicles in COVID-19-induced ARDS: Mechanisms of action, research progress, challenges, and opportunities

https://doi.org/10.1016/j.intimp.2021.107694Get rights and content

Highlights

  • MSC therapy can attenuate cytokine storm and enhance alveolar fluid clearance.

  • MSC-derived EVs impede cytokine overproduction leading to immunity reconstitution.

  • Exosomes seem to be safer as they cannot form a tumor or lead to emboli formation.

  • Source of MSC, administration route, and optimal dose should be carefully evaluated.

  • Clinical-grade production and stability during MSC preparation are major challenges.

Abstract

In late 2019, a novel coronavirus (SARS-CoV-2) emerged in Wuhan city, Hubei province, China. Rapidly escalated into a worldwide pandemic, it has caused an unprecedented and devastating situation on the global public health and society economy. The severity of recent coronavirus disease, abbreviated to COVID-19, seems to be mostly associated with the patients’ immune response. In this vein, mesenchymal stromal/stem cells (MSCs) have been suggested as a worth-considering option against COVID-19 as their therapeutic properties are mainly displayed in immunomodulation and anti-inflammatory effects. Indeed, administration of MSCs can attenuate cytokine storm and enhance alveolar fluid clearance, endothelial recovery, and anti-fibrotic regeneration. Despite advantages attributed to MSCs application in lung injuries, there are still several issues __foremost probability of malignant transformation and incidence of MSCs-related coagulopathy__ which should be resolved for the successful application of MSC therapy in COVID-19. In the present study, we review the historical evidence of successful use of MSCs and MSC-derived extracellular vesicles (EVs) in the treatment of acute respiratory distress syndrome (ARDS). We also take a look at MSCs mechanisms of action in the treatment of viral infections, and then through studying both the dark and bright sides of this approach, we provide a thorough discussion if MSC therapy might be a promising therapeutic approach in COVID-19 patients.

Keywords

Mesenchymal stem cells
Extracellular vesicles
COVID-19
SARS-CoV-2
Acute respiratory distress syndrome
Immunomodulation

Abbreviations

ACE2
Angiotensin-Converting Enzyme 2
AD-MSC
Adipocyte-Derived MSC
AFC
Alveolar Fluid Clearance
ALI
Acute Lung Injury
ALT
Alanine Aminotransferase
Ang-1
Angiopoietin-1
ARDS
Acute Respiratory Distress Syndrome
AST
Aspartate Aminotransferase
AT II
Type II Alveolar Epithelial
BDNF
Brain-Derived Neutrophilic Factor
BM-MSC
Bone Marrow MSC
COPD
Chronic Obstructive Pulmonary Disease
CRP
C-Reactive Protein
CT
Computerized Tomography
DC
Dendritic Cell
DIC
Disseminated Intravascular Coagulation
EV
Extracellular Vesicle
GVHD
Graft-Versus-Host Disease
hESC
Human Embryonic Stem Cell
HGF
Hepatocyte Growth Factor
HIF1-α
Hypoxia-Induced Factor 1-Α
IFN
Interferon
IMRC
Immunity and Matrix-Regulatory Cell
IPF
Idiopathic Pulmonary Fibrosis
ISG
Interferon-Stimulated Genes
IV
Intravenous
KGF
Keratinocyte Growth Factor
LDH
Lactate Dehydrogenase
LIF
Leukemia Inhibitory Factor
LPS
Lipopolysaccharide
MERS-CoV
The Middle East Respiratory Syndrome Coronavirus
MIP-2
Macrophage Inflammatory Protein-2
MOD
Multiple Organ Dysfunction
MSC
Mesenchymal Stromal/Stem Cell
MVB
Multi Vesicle Body
NGF
Nerve Growth Factor
NK cell
Natural Killer Cell
PDGF
Platelet-Derived Growth Factor
PGE2
Prostaglandin E2
ROS
Reactive Oxygen Species
SARS-CoV
Severe Acute Respiratory Syndrome Coronavirus
SPA
Surfactant Protein A
SPC
Surfactant Protein C
TGF-β
Transforming Growth Factor-Β
Th
T Helper
TMPRSS2
Transmembrane Protease Serine 2
TNF- α
Tumor Necrosis Factor- Α
UC-MSC
Umbilical Cord MSC
VEGF
Vascular Endothelial Growth Factor
WBC
White Blood Cell

Cited by (0)

View Abstract