MCP-1 Priming Enhanced the Therapeutic Effects of Human Mesenchymal Stromal Cells on Contact Hypersensitivity Mice by Activating the COX2-PGE2/STAT3 Pathway

Liu, Qiuli; Ji, Suyun; Xia, Tingting; Liu, Jialing; Liu, Zhuojie; Zang, Zhijun

doi:10.1089/scd.2020.0035

Cited by 14 publications

(9 citation statements)

References 35 publications

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“…Other researchers indicate that MSCs treated with TNF-α possess enhanced angiogenic and osteogenic activity in vitro and in vivo [ 62 , 63 , 64 , 65 ]. MCP-1 priming was also shown to enhance the therapeutic effects of MSCs in contact-hypersensitive mice by activating the COX2-PGE2 pathway [ 66 ].…”

Section: Discussionmentioning

confidence: 99%

Equilibrium among Inflammatory Factors Determines Human MSC-Mediated Immunosuppressive Effect

Suzdaltseva

Goryunov

Silina

et al. 2022

Cells

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Mesenchymal stem cells (MSCs) are thought to be a promising therapeutic agent due to their multiple paracrine and immunomodulatory properties, providing protection from chronic inflammation and promoting tissue repair. MSCs can regulate the balance of pro-inflammatory and anti-inflammatory factors in inflamed tissues, creating a microenvironment necessary for successful healing; however, their interactions with immune cells are still poorly studied. We examined the temporal and spatial changes in gene regulation and the paracrine milieu accompanying the MSC-mediated immunosuppression effect in mixed cultures with activated peripheral blood mononuclear cells (PBMCs). Our data reveal that the peak of suppression of PBMC proliferation was achieved within 48 h following co-culture with MSCs and subsequently did not undergo a significant change. This effect was accompanied by an increase in COX-2 expression and an induction of IDO synthesis in MSCs. At this point, the expression of IL-1, IL-6, IL-8, IFN-γ, MCP-1, and G-CSF was upregulated in co-cultured cells. On the contrary, we observed a decrease in the concentrations of IL-10, IL-13, IL-5, and MIP-1b in co-culture supernatants compared to intact cultures of activated PBMCs. The regulation of IDO, IL-1, IL-6, and G-CSF production was accomplished with the involvement of direct cell–cell contact between MSCs and PBMCs. These findings provide new insights into the use of potential precondition inducers or their combinations to obtain functionally qualified MSCs for more effective treatment of inflammatory diseases.

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Section: Discussionmentioning

confidence: 99%

Equilibrium among Inflammatory Factors Determines Human MSC-Mediated Immunosuppressive Effect

Suzdaltseva

Goryunov

Silina

et al. 2022

Cells

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“…When MSCs are stimulated by cytokines, the NF-κB pathway in MSCs is activated. Accordingly, their downstream immunomodulatory proteins and chemokine receptors will be overexpressed [ 42 , 47 , 72 – 74 ]. This means that the targeted migration response to the chemokine capacity of MSCs is strengthened and the MSC homing efficiency is enhanced after cytokine priming [ 47 , 74 , 75 ].…”

Section: Discussionmentioning

confidence: 99%

“…This means that the targeted migration response to the chemokine capacity of MSCs is strengthened and the MSC homing efficiency is enhanced after cytokine priming [ 47 , 74 , 75 ]. These factors can enhance the immunomodulatory capacities of immune cells and restore the inflammatory microenvironment [ 72 , 74 , 76 ]. The expression of cytokines, such as IL-1β, TNF-α, and MIF, are boosted in inflammatory lesions and the body and recruit a large number of immune cells to maintain the inflammatory microenvironment [ 77 , 78 ].…”

Section: Discussionmentioning

confidence: 99%

IL-1β-primed mesenchymal stromal cells exert enhanced therapeutic effects to alleviate Chronic Prostatitis/Chronic Pelvic Pain Syndrome through systemic immunity

et al. 2021

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Background Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects patient health. Despite the elusiveness of innate therapeutic effects, mesenchymal stromal cells (MSCs) hold great promise for inflammation-related diseases. Recent evidence indicates that disease-specific inflammatory cytokines could enhance the therapeutic effects of MSCs. Methods By establishing a CP/CPPS mouse model and pretreating MSCs with the cytokine interleukin-1β (IL-1β), we studied the IL-1β-primed MSC immunoregulatory ability and targeted migration ability in vitro and in CP/CPPS mice. Results IL-1β levels significantly increased in the prostate tissue and serum of experimental autoimmune prostatitis (EAP) mice. Pretreatment with IL-1β enhanced the immunomodulatory potential and targeted migration of MSCs in vitro. Furthermore, intravenous infusion of IL-1β-primed MSCs dampened inflammation in prostate tissues and alleviated hyperalgesia in EAP mice. The infused MSCs inhibited monocyte infiltration and promoted regulatory T lymphocyte formation in prostate tissue, thus remodeling the local environment. Surprisingly, IL-1β-primed MSCs exhibited improved accumulation in the spleen but not in prostate tissue. Accordingly, infused MSCs reshaped systemic immunity by reducing the proportion of Ly6ChighCD11b+ monocytes and boosting the proportion of CD4+Foxp3+ regulatory T lymphocytes in the spleen and lung. Inflammatory chemokine (C–C motif) ligand 2 (CCL2) decreased through the downregulation of the NF-κB and JNK/MAPK pathways by inflammatory resolution via MSCs infusion to alleviate pain. Conclusion In summary, IL-1β-primed MSCs restored systemic immunologic homeostasis to alleviate CP/CPPS by modulating systemic immunity. These findings provide a novel strategy to boost the therapeutic effects of MSC-based therapy for CP/CPPS and reveal the essential role of systematic immunity in the treatment of CP/CPPS with MSC infusion.

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“…When MSCs are stimulated by cytokines, the NF-κB pathway in MSCs is activated. Accordingly, their downstream immunomodulatory proteins and chemokine receptors will be overexpressed [42,47,[72][73][74]. This means that the targeted migration response to the chemokine capacity of MSCs is strengthened and the MSC homing e ciency is enhanced after cytokine priming [47,74,75].…”

Section: Discussionmentioning

confidence: 99%

“…This means that the targeted migration response to the chemokine capacity of MSCs is strengthened and the MSC homing e ciency is enhanced after cytokine priming [47,74,75]. These factors can enhance the immunomodulatory capacities of immune cells and restore the in ammatory microenvironment [72,74,76]. The expression of cytokines, such as IL-1β, TNF-α, and MIF, are boosted in in ammatory lesions and the body and recruit a large number of immune cells to maintain the in ammatory microenvironment [77,78].…”

Section: Discussionmentioning

confidence: 99%

IL-1β Primed Mesenchymal Stromal Cells Alleviate Chronic Prostatitis/chronic Pelvic Pain Syndrome Through Systemic Immunity

Liu

Zhu

Chi

et al. 2021

Preprint

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Background: Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) seriously affects patient health. Despite the elusiveness of innate therapeutic effects, mesenchymal stromal cells (MSCs) hold great promise for inflammation-related diseases. Recent evidence indicates that disease-specific inflammatory cytokines could enhance the therapeutic effects of MSCs.Methods: By establishing a CP/CPPS mouse model and pretreating MSCs with the cytokine interleukin-1β (IL-1β), we studied the IL-1β-primed MSC immunoregulatory ability and targeted migration ability in vitro and in CP/CPPS mice.Results: IL-1β levels significantly increased in the prostate tissue and serum of experimental autoimmune prostatitis (EAP) mice. Pretreatment with IL-1β enhanced the immunomodulatory potential and targeted migration of MSCs in vitro. Furthermore, intravenous infusion of IL-1β-primed MSCs dampened inflammation in prostate tissues and alleviated hyperalgesia in EAP mice. The infused MSCs inhibited monocyte infiltration and promoted regulatory T lymphocyte formation in prostate tissue, thus remodeling the local environment. Surprisingly, IL-1β-primed MSCs exhibited improved accumulation in the spleen but not in prostate tissue. Accordingly, infused MSCs reshaped systemic immunity by reducing the proportion of Ly6ChighCD11b+ monocytes and boosting the proportion of CD4+Foxp3+ regulatory T lymphocytes in the spleen and lung. Inflammatory chemokine (C-C motif) ligand 2 (CCL2) decreased through the downregulation of the NF-κB and JNK/MAPK pathways by inflammatory resolution via MSCs infusion to alleviate pain.Conclusion: In summary, IL-1β primed MSCs restored systemic immunologic homeostasis to alleviate CP/CPPS by modulating systemic immunity. These findings provide a novel strategy to boost the therapeutic effects of MSC-based therapy for CP/CPPS and reveal the essential role of systematic immunity in the treatment of CP/CPPS with MSC infusion.

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MCP-1 Priming Enhanced the Therapeutic Effects of Human Mesenchymal Stromal Cells on Contact Hypersensitivity Mice by Activating the COX2-PGE2/STAT3 Pathway

Cited by 14 publications

References 35 publications

Equilibrium among Inflammatory Factors Determines Human MSC-Mediated Immunosuppressive Effect

Equilibrium among Inflammatory Factors Determines Human MSC-Mediated Immunosuppressive Effect

IL-1β-primed mesenchymal stromal cells exert enhanced therapeutic effects to alleviate Chronic Prostatitis/Chronic Pelvic Pain Syndrome through systemic immunity

IL-1β Primed Mesenchymal Stromal Cells Alleviate Chronic Prostatitis/chronic Pelvic Pain Syndrome Through Systemic Immunity

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