From: Mesenchymal stem cells and their derived small extracellular vesicles for COVID-19 treatment
 | Molecular | Mechanisms of SARS-CoV-2 | Refs | Mechanisms of MSCs | Involved organs/diseases | Involved cell types | Origin of MSCs | Refs. |
---|---|---|---|---|---|---|---|---|
Common molecular | ACE2 and TMPRSS2 | SARS-CoV-2 enters target cells via its S protein which helps the virus to target ACE2 binding sites of cells, and the priming activator TMPRSS2 of ACE2 assists internalization of the virus | [51] | ACE2(-) and TMPRSS2(-) protect MSCs from infecting by SARS-CoV-2 | Lung | Immune cells | BMMSCs, ADMSCs, UC-MSCs, etc | |
ACE2 overexpressing MSCs decrease inflammatory factors and pyroptosis factors | Lung | AT-II and Beas-2B | UC-MSCs | [62] | ||||
Specific molecular | Tau protein | S protein of SARS-CoV-2 interacts with Tau protein | [64] | Regulate hyperphosphorylated Tau protein | Brain | Nerve cells | UC-MSCs | |
KIM-1 | KIM-1, a potential receptor of SARS-CoV-2, mediates and exacerbates the vicious circle of kidney infections by the virus | [49] | Reduce the KIM-1 level | Kidney | Â | BMMSCs | [70] | |
NLRP3 inflammasomes | The interplay between ACE2 receptor and SARS-CoV-2 S protein activates NLRP3 inflammasomes, thus facilitating inflammatory responses | [50] | Inhibit activation of inflammatory mediators and NLRP3 inflammasomes via exosomes | Intervertebral disc | Nucleus pulposus cells | BMMSCs | [71] | |
Block the NLRP3 inflammasome activation and inflammatory agents | Type 2 diabetes | Â | UC-MSCs | [72] | ||||
Control NLRP3 by facilitating the Hippo pathway of macrophages and regulating XBP1 | Liver | Macrophage | BMMSCs | [73] | ||||
Inhibit NLRP3 inflammasome activity via the anti-oxidative protein stanniocalcin-1 | Heart | HL-1 cells | BMMSCs | [74] | ||||
MAIT cells | SARS-CoV–2 activates and depletes MAIT cells that can kill bacteria or cells infected by viruses | [75] | Induce activated phenotypes and regulate activation of MAIT cells by up-regulating expressions of CD69, granzyme B, IFN-γ, and TNF-α | Infection, metabolic disorders, and inflammatory diseases | MAIT cells | ADMSCs | [76] |