Inflammatory cytokines pre-treatment enhances the immunomodulatory property of hUC-MSCs
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PROVIDER: PRJNA930032 | ENA |
REPOSITORIES: ENA
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Project description:Mesenchymal stem cells (MSCs) exist in almost all tissues and participate in tissue regeneration and homeostasis. MSCs based therapy is applied to some refractory immune diseases to control inflammation, such as lupus nephritis, Crohn’s disease and rheumatoid arthritis. However, accumulating studies showed that the immunomodulatory capacity of naïve MSCs is mild and limited. To enhance MSCs immunomodulatory function, researchers innovated a new method to reprogram MSCs via pre-treatment with inflammatory cytokines. In this work, we firstly used a cocktail of three cytokines, IL-1β, TNF-a and IFN-γ, to treat hUC-MSCs (human MSCs from umbilical cord). We then performed gene expression profiling analysis using data obtained from RNA-seq of 3 untreated hUC-MSCs (ctrl) and 3 cytokines-treated hUC-MSCs (primed).
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Project description:Peripheral infusion of human umbilical cord mesenchymal stem cells (hUC-MSCs) can profoundly suppress the activation of c-Mos and remarkably improve hepatic histology, suppress the systemic inflammatory reaction, and promote animal survival in a large non-human primate model of acute liver failure (ALF). The mechanism through which hUC-MSCs inhibits c-Mos activation in vivo remains unclear. We hypothesized that hUC-MSCs can adaptively produce certain inhibitory cytokines in response to the pro-inflammatory microenvironment. To confirm this, we stimulated cultured hUC-MSCs with inflammatory monkey serum (serum isolated at day 1 following toxin challenge). After a 30-min stimulation, the cells were collected for microarray gene expression analysis. A whole human genome oligo microarray analysis was performed to reveal the altered gene expression profiles of the hUC-MSCs
2016-05-12 | E-MTAB-4750 | biostudies-arrayexpress
Project description:Intrauterine adhesion (IUA), characterized by endometrial fibrosis, is a common cause of female reproductive disorders. IUA-like mice model was created with curettage plus LPS stimulation to mimic endometrial fibrosis in IUA patients. Mesenchymal stem cells (MSCs) based therapy is applied to some refractory immune diseases to control inflammation and their immunomodulatory function can be enhanced via pre-treatment with inflammatory cytokines. In this work, we examined the effect of untreated and cytokines primed MSCs therapy on macrophage in IUA-like mice model. The uteri samples were collected from sham, IUA modeling, IUA+control MSCs treatment and IUA+primed MSCs treatment groups of mice. Endometrial macrophages were sorted through F4/80 magnetic beads and performed RNA-seq.
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Project description:Human umbilical cord mesenchymal stem cells (hUC-MSCs) are broadly applied in clinical treatment due to easy availability, low immunogenicity, and no ethical issues involved. However, the microenvironment of inflammatory tissues may cause oxidative stress and induce senescence in transplanted hUC-MSCs, which will further reduce the proliferation, migration ability, and the final therapeutic effects of hUC-MSCs. Beta-nicotinamide mononucleotide (NMN), and coenzyme Q10 (CoQ10) are famous antioxidants and longevity medicines that could reduce intracellular reactive oxygen species levels by different mechanisms.Transcriptomic analysis revealed that NMN and CoQ10 both increased DNA repair ability and cyclin expression, and downregulated TNF and IL-17 inflammatory signaling pathways, thereby contributed to the proliferation of advanced stem cells and aging due to oxidative stress. These findings suggest that antioxidants can improve the survival and efficacy of hUC-MSCs in stem cell therapy for inflammation-related diseases.
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Project description:Neuromyelitis optica (NMO) is a severe autoimmune inflammatory disease of the central nervous system that affects motor function and causes relapsing disability. Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) have been used extensively in the treatment of various inflammatory diseases, due to their potent regulatory roles that can mitigate inflammation and repair damaged tissues. However, their use in NMO is currently limited, and the mechanism underlying the beneficial effects of hUC-MSCs on motor function in NMO remains unclear. In this study, we investigate the effects of hUC-MSCs on the recovery of motor function in an NMO systemic model. Our findings demonstrate that milk fat globule epidermal growth 8 (MFGE8), a key functional factor secreted by hUC-MSCs, plays a critical role in ameliorating motor impairments. We also elucidate that the MFGE8/Integrin αvβ3/NF-κB signaling pathway is partially responsible for structural and functional recovery, in addition to motor functional enhancements induced by hUC-MSC exposure. Taken together, these findings strongly support the involvement of MFGE8 in mediating hUC-MSCs-induced improvements in motor functional recovery in an NMO mouse model. In addition, this provides new insight on the therapeutic potential of hUC-MSCs and the mechanisms underlying their beneficial effects in NMO.
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Project description:hUC-MSCs exhibit the biological characteristics and potential for neural differentiation.The different gene involved in the neural differentiation were not clear. We used microarrays to detail the global programme of gene expression underlying cellularisation and identified distinct classes of up-regulated genes during the process of neural differentiation.
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Project description:Effect of Inflammatory cytokines primed hUC-MSCs therapy on gene expression of macrophages in IUA-like mice model
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Project description:Bone marrow mesenchymal stromal cells (MSCs) regulate homeostasis and trafficking of cells of the blood lineage. In response to traumatic injury or infection, MSCs are believed to mobilize from the bone marrow, but it is largely unknown how egress into circulation impacts MSC function. Here we show that biomechanical forces associated with trafficking of MSCs from the bone marrow into the vasculature contribute uniquely to genetic signaling that reinforces MSC repression of immune cell activation. Laminar wall shear stress (LSS) typical of fluid frictional forces present on the lumen of arterioles stimulates increases in antioxidant and anti-inflammatory mediators, as well as an array of chemokines capable of immune cell recruitment. Importantly, LSS promotes a signaling cascade through COX2 that elevates prostaglandin E2 (PGE2) biosynthesis, permitting MSCs to suppress immune cell activation in the presence of inflammatory cues. Pharmacological inhibition of COX2 depleted PGE2 and impaired the ability of MSCs to block tumor necrosis factor-α (TNF-α) production, supporting a key role for PGE2 in the MSC immunomodulatory response to LSS. Preconditioning of MSCs by LSS ex vivo was an effective means of enhancing therapeutic efficacy in a rat model of traumatic brain injury, as evidenced by decreased numbers of apoptotic and M1-type activated microglia in the hippocampus and by retention of endogenous MSCs in the bone marrow. We conclude that biomechanical forces provide critical cues to MSCs residing at the vascular interface which influence MSC immunomodulatory and paracrine functions, thus providing unique opportunities for functional enhancement of MSCs used in therapeutic applications.
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Project description:HUC model includes three cell lines: HUC-BC, HUC-PC, and MCT11. They were all originally derived from human uroepithelium. However, three cell lines have different malignant potential. We here performed micro array to examine the differences in gene expression among three cell lines.
2020-10-20 | E-MTAB-9699 | biostudies-arrayexpress
Project description:Mesenchymal stem cells (MSCs) have garnered attention for their regenerative and immunomodulatory capabilities in clinical trials for various diseases. However, the effectiveness of MSC-based therapies, especially for conditions like graft-versus-host disease (GvHD), remains uncertain. The cytokine IFN-γ has been known to enhance the immunosuppressive properties of MSCs through cell-to-cell interactions and soluble factors. In this study, we observed that IFN-γ-treated MSCs upregulated the expression of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), associated with immune evasion through the inhibition of NK cell cytotoxicity. To co-opt this immunomodulatory function, we generated MSCs overexpressing CEACAM1 and found that CEACAM1-engineered MSCs significantly reduced NK cell activation and cytotoxicity, independent of NKG2D ligand regulation. Furthermore, CEACAM1-engineered MSCs effectively inhibited the proliferation and activation of T cells along with the inflammatory responses of monocytes. In a humanized GvHD mouse model, CEACAM1-MSCs, particularly CEACAM1-4S-MSCs, demonstrated therapeutic potential by improving survival and alleviating symptoms. These findings suggest that CEACAM1 expression on MSCs contributes to MSC-mediated regulation of immune responses and that CEACAM1-engineered MSC could have therapeutic potential in conditions involving immune dysregulation.
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