Lipopolysaccharides Shapes the Human Wharton's Jelly-Derived Mesenchymal Stem Cellsin Vitro

Abstract

Background: Although the expression of toll-like receptors (TLRs) on different types of human mesenchymal stem cells (hMSCs) has recently been reported, controversy remains regarding the presence of TLR4 as well as its engagement and impact on human Wharton's jelly-derived MSCs (hWJ-MSCs). Methods: In the present study, the expression and role of TLR4 in hWJ-MSCs was investigated using a model of lipopolysaccharide (LPS). Proliferation, apoptosis, and the expression of paracrine factors in hWJ-MSCs primed with LPS were analysed. Results: The expression of TLR4 was high at the RNA level but very low at the protein level. hWJ-MSCs responded to LPS stimulation and initiated a marked up-regulation of inflammatory cytokine (IL-1α, IL-1β, IL-6, and IL-8) production. Moreover, hWJ-MSCs LPS stimulation resulted in the up-regulation of indoleamine 2,3-dioxygenase [IDO]-1, Cox2, interferon [IFN]-β, and matrix metalloproteinase (MMP)-2 but a down-regulation of MMP-9, which affect the immunosuppressive potential of hWJ-MSCs. Conclusions: These data suggest that LPS engagement shapes hWJ-MSCs and results in the production of pro-inflammatory cytokines and inhibitory immune mediators, showing TLR4 agonist induces the hWJ-MSCs polarization to a pro-inflammatory and immunosuppressive state, which may be beneficial for the exploration of the clinical potential of hWJ-MSCs.

Human Bone Marrow-Derived Mesenchymal Stromal Cells Differentially Inhibit Cytokine Production by Peripheral Blood Monocytes Subpopulations and Myeloid Dendritic Cells

“…Finally, we evaluated protein and mRNA expression in nonstimulated MSC and after LPS and/or IFN γ treatment, in order to understand how their regulatory function could be affected. As previously described, we found a slight increase in the mRNA of the proinflammatory cytokines TNF- α and IL-6, along with a significant increase in the chemotactic IL-8 [ 23 – 29 ] and the immunosuppressor IDO, ICOSL, and CD73 [ 26 , 30 , 31 ], upon stimulation with LPS + IFN γ . Of note, an increased expression of other immunoregulatory molecules, such as fibroblast growth factor 2 (FGF2), hepatocyte growth factor (HGF), cyclooxygenase 2 (COX2), prostaglandin E2 (PGE2), upon TLR4 stimulation had also been described in the literature [ 26 , 28 , 32 , 33 ].…”

Innate Immune Response of Human Embryonic Stem Cell‐Derived Fibroblasts and Mesenchymal Stem Cells to Periodontopathogens

“…Studies have shown that the immunomodulatory property of MSCs seems to depend on their origin, as differences between bone marrow, adipose tissue, and Wharton's jelly-derived MSCs were found recently [48, 49]. These studies demonstrated the resistance of Wharton's jelly-derived MSCs to bacterial challenge compared to other postnatal sources of MSCs.…”

Short-term memory of danger signals or environmental stimuli in mesenchymal stem cells: implications for therapeutic potential

“…6,7 In recent years, a number of pre-conditioning strategies have been used to boost MSC function and therapeutic potential. Such strategies include treatment with growth factors, 8,9 cytokines, [10][11][12] hypoxic shock, 13 HDLs, 14 lipopolysaccharide (LPS) 15 or chemical compounds. 16,17 Based on findings from these studies, pre-treatment greatly enhances cell survival and the potential to migrate to damaged or inflamed tissues, thereby markedly improving the efficacy of these cells in the treatment of certain diseases or in tissue repair in an injury-specific fashion.…”