Dental pulp stem cell-derived exosomes suppress M1 macrophage polarization through the ROS-MAPK-NFκB P65 signaling pathway after spinal cord injury

Abstract

Stem cell-derived exosomes have recently been regarded as potential drugs for treating spinal cord injury (SCI) by reducing reactive oxygen species (ROS) and suppressing M1 macrophage polarization. However, the roles of ROS and exosomes in the process of M1 macrophage polarization are not known. Herein, we demonstrated that ROS can induce M1 macrophage polarization and have a concentration-dependent effect. ROS can induce M1 macrophage polarization through the MAPK-NFκB P65 signaling pathway. Dental pulp stem cell (DPSC)-derived exosomes can reduce macrophage M1 polarization through the ROS-MAPK-NFκB P65 signaling pathway in treating SCI. This study suggested that DPSC-derived exosomes might be a potential drug for treating SCI. Disruption of the cycle between ROS and M1 macrophage polarization might also be a potential effective treatment by reducing secondary damage. Graphical Abstract

Biotransformation of Tyrosol into a Novel Valuable α-Galactoside with Increased Solubility and Improved Anti-inflammatory Activities

“…Excessive ROS generation mediates inflammatory signaling cascades in microglia through activation of the MAPK signaling pathway, which in turn led to the activation of NF-κB and expression of a variety of pro-inflammatory cytokines, such as TNF-α and IL-6. 36,37 The same phenomenon of the increased production of pro-inflammatory cytokines in the model was also observed in our study, while tyrosol and its galactoside showed inhibitory effects on these cytokines. In the presence of tyrosol, the mRNA level of TNFα was reduced to 73% of that in the Mod group, and the mRNA level of IL-6 was also slightly reduced (Figure 6G,H).…”

Exosomes combined with biomaterials in the treatment of spinal cord injury

“…Moreover, exosomes secreted by ADSCs under hypoxia preconditioning are potential therapeutic agents in SCI that promote M1/M2 polarization of microglia (Shao et al, 2020). Meanwhile, exosomes derived from dental pulp stem cells have strong immunomodulatory effects, but their efficacy in promoting neurological and motor functions is unknown, as few studies have been conducted to address their potential (Liu C. et al, 2022). In our previous studies, we have described that human menstrual blood-derived mesenchymal stem cells (MenSCs), when combined with biomaterials, can provide an optimized Frontiers in Bioengineering and Biotechnology frontiersin.org bionic microenvironment for spinal cord injury repair, thereby reducing the inflammatory response, promoting neuronal differentiation and improving motor function.…”

Applying stem cell therapy in intractable diseases: a narrative review of decades of progress and challenges

“…Using exosomes dental pulp stem cells (DPSCs), Liu and team demonstrated the therapeutic effects of exosomes in regulating inflammatory signals in mice afflicted with SCI ( 4 ). Post-infusion results showed that DPSCs decrease reactive oxygen species (ROS) levels and subsequently reduce M1 macrophage polarization in damaged tissues by suppressing the ROS-MAPK-FκB P65 signalling pathway.…”

“…Exosomes are extracellular vesicles released from stem cells that play a role in the mediation of cell-to-cell signalling through the release of paracrine factors, catalysing the repair and regeneration of neighbouring cells ( 3 ). Exosomes are also able to penetrate the blood-brain barrier and blood-spinal cord barrier with high transport efficiency and most importantly, without occluding microvessels as they are small-sized molecules ( 4 ). This cell-free therapy allows patients to benefit from the reparative effects of stem cells, without introducing living stem cells that can be potentially rejected by the body and have tumourigenic properties.…”