Mesenchymal stem cells immunomodulation: The road to IFN-γ licensing and the path ahead

Carvalho, Amandda Évelin Silva De; Sousa, Marielly Reis Resende; Alencar‐Silva, Thuany; Carvalho, Juliana Lott; Saldanha-Araújo, Felipe

doi:10.1016/j.cytogfr.2019.05.006

Cited by 63 publications

(49 citation statements)

References 135 publications

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“…Recently, several studies have been published demonstrating that the immunosuppressive functions of MSCs can be boosted by priming with recombinant inflammatory factors, especially IFN-γ, TNF-α, and IL-17 [22,23]. With this in mind, in this study, we interrogated whether the use of the plasma collected from GVHD patients might be an effective and innovative strategy to boost MSC immunomodulatory behavior.…”

Section: Discussionmentioning

confidence: 99%

“…MSCs promote the generation and expansion of regulatory T cells (Tregs) to control the immune response [23]. In order to determine if the MSC priming with GVHD plasma has any influence on this process, primed cells were cultured with phytohemagglutinin (PHA)-activated PBMCs for 5 days.…”

Section: Generation Of Regulatory T Cellsmentioning

confidence: 99%

“…Aiming to tackle such therapeutic limitation, several researchers have investigated priming (a.k.a licensing) strategies in order to enhance the immunosuppressive potential of MSCs, including peptides [20], agonists for Toll-like receptors [21], and proinflammatory recombinant factors [22], among which IFN-γ is the most intensively investigated molecule so far [23][24][25]. Still, in the first clinical investigation of IFN-γ-primed MSCs, data was disappointing, justifying further studies [26].…”

Section: Introductionmentioning

confidence: 99%

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GVHD-derived plasma as a priming strategy of mesenchymal stem cells

et al. 2020

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Background: Mesenchymal stem cell (MSC) therapy is an important alternative for GVHD treatment, but a third of patients fail to respond to such therapy. Therefore, strategies to enhance the immunosuppressive potential of MSCs constitute an active area of investigation. Here, we proposed an innovative priming strategy based on the plasma obtained from GVHD patients and tested whether this approach could enhance the immunosuppressive capacity of MSCs. Methods: We obtained the plasma from healthy as well as acute (aGVHD) and chronic (cGVHD) GVHD donors. Plasma samples were characterized according to the TNF-α, IFN-γ, IL-10, IL-1β, IL-12p40, and IL-15 cytokine levels. The MSCs primed with such plasmas were investigated according to surface markers, morphology, proliferation, mRNA expression, and the capacity to control T cell proliferation and Treg generation. Results: Interestingly, 57% of aGVHD and 33% of cGVHD plasmas significantly enhanced the immunosuppressive potential of MSCs. The most suppressive MSCs presented altered morphology, and those primed with cGHVD displayed a pronounced overexpression of ICAM-1 on their surface. Furthermore, we observed that the ratio of IFN-γ to IL-10 cytokine levels in the plasma used for MSC priming was significantly correlated with higher suppressive potential and Treg generation induction by primed MSCs, regardless of the clinical status of the donor. Conclusions: This work constitutes an important proof of concept which demonstrates that it is possible to prime MSCs with biological material and also that the cytokine levels in the plasma may affect the MSC immunosuppressive potential, serving as the basis for the development of new therapeutic approaches for the treatment of immune diseases.

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Section: Discussionmentioning

confidence: 99%

Section: Generation Of Regulatory T Cellsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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GVHD-derived plasma as a priming strategy of mesenchymal stem cells

et al. 2020

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“…Many studies have proved the therapeutic potential of mesenchymal stem cells (MSCs), multipotent cells isolated from various human tissues, in tissue repair; this therapeutic potential is attributable to the capacity of these cells to undergo multipotent differentiation and to modulate immune responses [20][21][22] . CV-MSCs that are capable of self-renewal and differentiation and that exhibit immunoregulatory properties can be isolated from human term placenta, which is abundant and commonly discarded after delivery 23 .…”

Section: Discussionmentioning

confidence: 99%

Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway

Chu

Yue

Wei

et al. 2020

Preprint

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Objectives Trophoblast dysfunction during pregnancy is fundamentally involved in preeclampsia. The aim of this study was to understand how human chorionic villous mesenchymal stem cells (CV-MSCs) operate in regulation of trophoblast function.Materials and Methods We treated trophoblasts with CV-MSC supernatant under hypoxic conditions, and transcriptome and pathway analyses of trophoblasts were performed. Western blotting and PCR analysis were used to examine the JAK2, STAT3 and autophagy associated protein expression levels in trophoblasts.Results The CV-MSC supernatant treatment markedly enhanced proliferation, invasion and autophagy. The RNA-seq revealed JAK2/STAT3 signalling as an upstream regulator, and STAT3 mRNA and protein levels increased during CV-MSC treatment. Inhibition of JAK2/STAT3 signalling reduced autophagy, survival and invasion of trophoblasts even in the presence of CV-MSCs, and blocking autophagy did not affect STAT3 activation in trophoblasts treated with CV-MSCs. Importantly, overexpression of STAT3 increased the levels of autophagy in trophoblasts; thus, it regulated positively autophagy in hypoxic trophoblasts. Human placental explants also proved our finding, in which STAT3 was activated and LC3B-II levels were increased by CV-MSC treatment.Conclusions Our data suggest that CV-MSC-dependent activation of JAK2/STAT3 signalling is a prerequisite for upregulation of autophagy in trophoblasts.

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“…Interferon-gamma rays were investigated as a means of licensing for MSCs and it was found that interferon-gamma ray licensing enhances MSCs' immunomodulatory properties. Interferon-gamma licensing of MSCs was also found to decrease cell death when preserved via cryopreservation and following the actual infusion [33]. Comparisons of MSC compared to HSC has found MSC to be significantly safer, as one review found HSCT to cause lupus erythematosus, BK virus infection, fever, chest pain, renal function impairment, and sometimes death [34].…”

Section: Mesenchymal Stem Cellsmentioning

confidence: 99%

Crohn’s Disease: Hematopoietic and Mesenchymal Stem Cell Therapy as Potential Treatment

2020

JCRC

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Purpose: The purpose of this work was to comprehensively review literature to determine the safety and efficacy of stem cells for the treatment of Crohn’s disease and compare the effects of hematopoietic stem cells (HSCs) to that of mesenchymal stem cells (MSCs). Results: The data search included 5 animal models and clinical trials found on PubMed. The 5 studies included for HSCs and the 15 trails for MSCs found them to be a safe and effective as a treatment option (allogeneic and autologous bone marrow and adipose derived) for CD except for one multicenter randomized trial for HSC therapy. Most trials investigate the impact of stem cells specifically on perianal fistula, a common occurrence in patients with CD. Conclusion: While both HSCs and MSCs proved their safety and efficacy, MSC studies showed a greater therapeutic effect over HSCs. Adipose MSCs and Bone Marrow Derived MSCs reached similar clinical healing rates, with studies backing support for both sides. Across the board, autologous stem cell transplants proved to be safer and more effective compared to their allogeneic counterparts.

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Mesenchymal stem cells immunomodulation: The road to IFN-γ licensing and the path ahead

Cited by 63 publications

References 135 publications

GVHD-derived plasma as a priming strategy of mesenchymal stem cells

GVHD-derived plasma as a priming strategy of mesenchymal stem cells

Chorionic villus-derived mesenchymal stem cell-mediated autophagy promotes proliferation and invasiveness of trophoblasts under hypoxia by activating the JAK2/STAT3 signalling pathway

Crohn’s Disease: Hematopoietic and Mesenchymal Stem Cell Therapy as Potential Treatment

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