Table 1 Pathologies involved in COVID-19 infection and MSC mechanisms to counteract the infection damages
Organs/tissue | SARS-CoV-2 associated pathologies | Mechanisms of MSC action |
|---|---|---|
Respiratory tract | Immune system exacerbation Cytokine storm Secondary infection (microbial invasion) Pulmonary architecture damages Pulmonary fibrosis | Immunomodulation -Inhibit innate immune cell activation (NK, DC, neutrophils, macrophages) -Inhibit adaptive immune cell proliferation and activation (T and B cells) -Immunomodulatory molecules release (HGF, IDO, PGE2) Anti-inflammation -Anti-inflammatory cytokine release (IL-10, TGF-β) -Increase Treg and Th22 cells -Induce M2 macrophages phenotype Antibacterial effect -Release antibacterial peptide (LL-37) Regeneration -Induce neovascularization -Stimulate local stem cell differentiation and proliferation -Secrete angiopoietin-1 and FGF-7 -Increase bioenergetic levels through mitochondrial transfer Fibrosis reduction -Inhibit TGF-β1 and collagen deposition in the lungs |
Heart | Myocarditis Arrhythmia Acute coronary syndrome Coagulopathies Kawasaki syndrome | Immunomodulation -Reduce IL-1β, IL-12, IL-17, C–C motif chemokine ligand 5, INF-ϒ, and TNF-α levels -Polarize macrophages towards an anti-inflammatory state Antiapoptotic effect -Reduce apoptosis of cardiomyocytes Fibrosis reduction Neoangiogenic effect -Enhance angiogenesis |
Liver | Cholestasis Hepatitis | Immunomodulation Immunomodulation of T helper (Th) cells Reduction of TNF-α, cytokeratin 19, metallopeptidase 9 and MCP-1 Improvement of monocyte infiltration in bile ducts |
Kidneys | Acute kidney injury (AKI) | Immunomodulation Inhibition of apoptosis Promotion of angiogenesis Nephroprotective effects Regeneration of renal tubular cells through MSC-derived EVs |
Digestive tract | Gastrointestinal (GI) alterations Deep alterations in gut microbiota | Inflammation regulation Induce the restoration of composition and diversity of colonic bacteria Promote tissue remodeling Induce eradication of pathogenic bacteria |
Central nervous system | Stroke Headache Epileptic seizures Depression Encephalitis Dizziness Guillain-Barre syndrome | Immunomodulation Promote angiogenesis Induce neuroprotection. Re-establishment of neural circuit Help to reduce viral invasion Induce reprogramming of microglia from M1 to M2 phenotype Downregulate TNF-α, IL-1β, and IL-6 |