Table 2 Anti-inflammatory mechanisms of MSCs

From: Mesenchymal stem cells: environmentally responsive therapeutics for regenerative medicine

Target cell Mechanism Primary effect Secondary effect
Dendritic cells PGE2/direct contact ↓ TNF-α, IL-12, differentiation and activation Impairs effect on resting NK cells
↓ T-cell proliferation
↓ INF-γ by TH1 cellsa
  PGE2, IL-6, IL-8 and SDF-1 ↑ IL-10 ↑ IL-4 by TH2 cellsa
Immature Dendritic cells PGE2 ↑ IL-10 ↑ Treg production,
↑ IL-10 by Treg cells
T cells (CD4+, helper T cells) PGE2, IDO, HGF, TGF-β1 and NO ↓ CD4+ T-cell proliferation by S-phase entry block and Go/G1 phase arrest
Inhibits T-cell functions
↓ B-cell proliferation
↓ Ig antibody production by B cells
  IL-10 Inactivate TH1 cells  
T cells (CD8+, cytotoxic T cells) sHLA-G5 ↓ cytotoxicity  
Treg cells IL-10 ↑ Treg production
↑ IL-10 by Treg cells
 
  sHLA-G5 ↓ Treg differentiation  
B cells PGE2, HGF, TGF-β1, IDO, NO and PD-L1 ↓ B-cell proliferation by Go/G1 phase arrest
↓ Ig antibody production by B cells,
↓ B-cell chemotaxis
 
NK cells PGE2, IDO, sHLA-G5, HGF, TGF-β1 ↓ INF-γ
↓ NK cell proliferation
↓ cytotoxicity
 
Monocytes PGE2 ↓ Monocyte proliferation by Go/G1 phase arrest
↓ Monocyte difference to DC
 
Macrophages IL-6 ↓ TNF-α  
  TSG-6 ↓ NF-kB ↓ TNF-α and IL-1
↓ MMP synthesis
  PGE2 Converts M1 (pro-inflammatory) type to M2 (anti-inflammatory) type macrophages ↓ IL-10
↓ IL-12
↓ TNF-α
Neutrophils IL-6 ↓ respiratory burst
↓ apoptosis
 
No specific target VEGF Pro-angiogenic Increased nutrient, O2 and waste transport
  IL-1Ra Antagonizes IL-1  
  sTNF-R Inhibits TNF-α production ↓ T-cell proliferation,
↓ INF-γ by TH1 cellsa
  1. Abbreviations: HGF, hepatocyte growth factor; HLA, human leukocyte antigen; IDO, indoleamine 2,3-dioxygenase; IL-1Ra, IL-1 receptor antagonist; INF, interferon; MMP, matrix metalloproteinase; NF-κB, nuclear factor kappa-light-chain-enhancer of activated B cell; NK, natural killer; NO, nitrous oxide; PD-L1, programmed cell death ligand-1; PGE2, prostaglandin 2; SDF-1, stromal cell-derived factor-1; sTNF-R, soluble TNF-α receptor; TGF, transforming growth factor; TNF, tumor necrosis factor; TSG, tumor necrosis alpha-stimulating gene; VEGF, vascular endothelial growth factor.
  2. aPromotes TH1→TH2 T-cell transition.