The biological changes of umbilical cord mesenchymal stem cells in inflammatory environment induced by different cytokines

Abstract

Mesenchymal stem cells (MSCs) are used as therapeutic tool for the treatment of immune diseases. The inflammatory environment also influences the characteristics of MSCs after transplantation. The aim of the study was to investigate the effects of pro-inflammatory cytokines on the characteristics of umbilical cord mesenchymal stem cells (UCMSCs). UCMSCs were exposed to pro-inflammatory cytokines in vitro for 3 and 7 days, and the biological properties were analyzed. The results showed that the proliferation ability was suppressed by interferon-γ (IFN-γ), tumor necrosis factor-α (TNF-α), and interleukin-1β (IL-1β). The adipogenic capacity was inhibited in all conditioned medium, while the chondrogenic and osteogenic capacity was enhanced by TNF-α and IL-1β in vitro. Prostaglandin E2 (PGE2) was increased by IL-1β on the third day, and angiopoietin-1 (Ang-1) was inhibited appreciably by TNF-α on the seventh day. Interleukin-6 (IL-6) was increased by TNF-α and IL-1β, and hepatocyte growth factor (HGF) was inhibited by all inflammatory cytokines. IFN-γ secretion level from human peripheral mononuclear cells (hPBMCs) was lowered by UCMSCs which had been stimulated by TNF-α or IL-1β for 3 days. Moreover, IFN-γ and TNF-α secretion level was only inhibited by UCMSCs which had been by stimulated IFN-γ for 3 days but not 7 days. Our data demonstrated that different inflammatory cytokines and the duration of treatment had different effects on the properties of UCMSCs, which might be instructive for clinical pretreatment in cellular therapeutics.

Genetically Modified Mouse Mesenchymal Stem Cells Expressing Non-Structural Proteins of Hepatitis C Virus Induce Effective Immune Response

“…Several authors have noted an increase in the antigen-presenting properties of MSCs as a result of IFN-γ pretreatment [72]. Other studies have shown that the "priming" of MSCs in vitro with IFN-γ, TNF-α, or IL-1β leads to the formation of the immunosuppressive phenotype MSC-2 [47,73,74]. Our results showed, for the first time, that after administration in mice, modified MSCs treated with IFN-γ cause a pronounced (tenfold) decrease in the cellular response.…”

Inflammatory niche: Mesenchymal stromal cell priming by soluble mediators

“…Regarding the effects of IL-1β priming on MSCs proliferation and differentiation, heterogeneous results have been reported (Figure 1 ). Namely, while IL-1β preconditioning increases equine AT-MSCs and human synovium-derived MSCs proliferation[ 65 , 66 ], exposure of UC-MSCs to IL-1β results in suppressed proliferation[ 67 ]. Moreover, functional analyses of human BM-MSCs have revealed that treatment with IL-1β does not affect the proliferation of these cells, and promotes their migration and adhesion to extracellular matrix components[ 68 ].…”

“…Sonomoto et al[ 70 ] demonstrated the ability of IL-1β to induce the osteogenic differentiation of human BM-MSCs via the Wnt pathway. Increased osteogenesis has also been found for equine AT-MSCs and human UC-MSCs treated with IL-1β[ 65 , 67 ]. On the other hand, depending on the concentration, IL-1β exerts dual effects on the osteogenesis of periodontal ligament-MSCs, since low doses of IL-1β promote osteogenesis by activating the bone morphogenetic protein (referred to as BMP)/Smad signaling pathway, while higher doses of the cytokine impede osteogenesis[ 71 ].…”

Honey‐incorporated nanofibre reduces replicative senescence of umbilical cord‐derived mesenchymal stem cells

“…Under in vitro conditions, repetitive passaging [2], and endogenous reactive oxygen species (ROS) and DNA damage [5] are associated with stem cell senescence. Moreover, the presence of an inflammatory microenvironment both in vitro or in vivo can induce cellular senescence [6]. On the other hand, a hypoxic condition has shown to preserve stem cell integrity in long‐term cultures [7].…”