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Table 2 Possible molecular mechanisms of MSCs against COVID-19

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

[58,59,60,61]

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

[65,66,67]

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

 

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

 

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]

  1. SARS-CoV-2 can damage the body through some specific mechanisms (Tau protein in brain, KIM-1 in kidney, and NLRP3 inflammasomes), in addition to the common ones (ACE2 and TMPRSS2). Overall, MSCs and sEVs protect the body through the above mechanisms to against COVID-19
  2. ACE2: angiotensin converting enzyme 2; TMPRSS2: transmembrane serine proteinase 2; KIM-1: kidney injury molecule-1; MAIT cells: mucosal-associated invariant T; MSCs: mesenchymal stem cells; BMMSCs: MSCs are derived from bone marrow; UC-MSCs or WJ-MSCs: ADMSCs: MSCs derived from adipose tissue