Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton

Adamo, Annalisa; Brandi, Jessica; Caligola, Simone; Delfino, Pietro; Tanasi, Ilaria; Carusone, Roberta; Cecconi, Daniela; Giugno, Rosalba; Manfredi, Marcello; Robotti, Elisa; Marengo, Emílio; Bassi, Giulio; Kamga, Paul Takam; Collo, Giada Dal; Gatti, Alessandro; Mercuri, Angela; Arigoni, Maddalena; Olivero, Martina; Calogero, Raffaele; Krampera, Mauro

doi:10.3389/fimmu.2019.00446

Cited by 67 publications

(64 citation statements)

References 96 publications

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“…We did not detect any differentially expressed pathway in primary MSCs and HS-5, except for the "Protein secretion" signature, thus suggesting that HS-5 cell line could help to characterize the molecular interactions between MSCs and cancer cells. Instead, HS-27A cell line could represent the negative control, as the majority of the gene signatures involved in the pro-tumor activity mediated by primary MSCs resulted down-modulated in this cell line, such as those regulating "angiogenesis, " "Wnt/β catenin signaling, " "KRAS signaling" and "PI3K-AKT-mTOR signaling" (Wang et al, 2015;El-Badawy et al, 2017;Poggi et al, 2018;Adamo et al, 2019a). The significant differences between HS-5 and HS-27A cell lines support the reliability of our method of comparison.…”

Section: Discussionmentioning

confidence: 99%

“…Among these, 19 resulted down-regulated and 5 up-regulated ( Figure 3B). Several pathways that have been reported to be involved in MSC-dependent pro-tumor activity displayed a strong up-regulation in primary MSCs compared to HS-27A cell line, including "angiogenesis, " "Wnt/β catenin signaling, " "KRAS signaling, " "PI3K-AKT-mTOR signaling, " and many others (Wang et al, 2015;El-Badawy et al, 2017;Poggi et al, 2018;Adamo et al, 2019a; Figure 3D). Conversely, HS-5 cell line and primary MSCs displayed a similar pathway expression profile.…”

Section: Hs-5 Cell Line Recapitulates the Ability Of Primary Mscs Tomentioning

confidence: 98%

“…Several recent studies have tried to characterize the molecular mechanisms underlying the interactions amongst IECs, cancer cells and MSCs (Whiteside, 2018;Adamo et al, 2019a;Wei et al, 2019). These efforts may allow to identify novel potential therapeutic targets not only in the field of inflammatory and autoimmune disease, but also in the context of solid tumors and hematological malignancies.…”

Section: Introductionmentioning

confidence: 99%

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HS-5 and HS-27A Stromal Cell Lines to Study Bone Marrow Mesenchymal Stromal Cell-Mediated Support to Cancer Development

Adamo

Delfino

Gatti

et al. 2020

Front. Cell Dev. Biol.

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In this study, we compared the overall gene and pathway expression profiles of HS-5 and HS-27A stromal cell lines with those of primary bone marrow MSCs to verify if they can be considered a reliable alternative tool for evaluating the contribution of MSCs in tumor development and immunomodulation. Indeed, due to their easier manipulation in vitro as compared to primary MSC cultures, several published studies took advantage of stromal cell lines to assess the biological mechanisms mediated by stromal cells in influencing tumor biology and immune responses. However, the process carried out to obtain immortalized cell lines could profoundly alter gene expression profile, and consequently their biological characteristics, leading to debatable results. Here, we evaluated the still undisclosed similarities and differences between HS-5, HS-27A cell lines and primary bone marrow MSCs in the context of tumor development and immunomodulation. Furthermore, we assessed by standardized immunological assays the capability of the cell lines to reproduce the general mechanisms of MSC immunoregulation. We found that only HS-5 cell line could be suitable to reproduce not only the MSC capacity to influence tumor biology, but also to evaluate the molecular mechanisms underlying tumor immune escape mediated by stroma cells. However, HS-5 pre-treatment with inflammatory cytokines, that normally enhances the immunosuppressive activity of primary MSCs, did not reproduce the same MSCs behavior, highlighting the necessity to accurately set up in vitro assays when HS-5 cell line is used instead of its primary counterpart.

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Section: Discussionmentioning

confidence: 99%

Section: Hs-5 Cell Line Recapitulates the Ability Of Primary Mscs Tomentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

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HS-5 and HS-27A Stromal Cell Lines to Study Bone Marrow Mesenchymal Stromal Cell-Mediated Support to Cancer Development

Adamo

Delfino

Gatti

et al. 2020

Front. Cell Dev. Biol.

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“…SC-EVs were observed to suppress B cell proliferation (30,80,81,108,120), activation (81,83) and migration (81) in order to induce anti-inflammatory immune responses. In vitro, SC-EVs have been observed to exert immunosuppressive effects by mediating differential mRNA expression of relevant genes in activated B cells (80) ( Table 1) or by downregulating PI3K-AKT signaling pathway and inhibiting actin activation in B cells via the delivery of miR-155-5p (81) ( Table 1).…”

Section: Stem Cell-derived Extracellular Vesicle Potential In B Cell/mentioning

confidence: 99%

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Xie

Wang²,

She

et al. 2020

Front. Immunol.

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Recent investigations on the regulatory action of extracellular vesicles (EVs) on immune cells in vitro and in vivo have sparked interest on the subject. As commonly known, EVs are subcellular components secreted by a paracellular mechanism and are essentially a group of nanoparticles containing exosomes, microvesicles, and apoptotic bodies. They are double-layer membrane-bound vesicles enriched with proteins, nucleic acids, and other active compounds. EVs are recognized as a novel apparatus for intercellular communication that acts through delivery of signal molecules. EVs are secreted by almost all cell types, including stem/progenitor cells. The EVs derived from stem/progenitor cells are analogous to the parental cells and inhibit or enhance immune response. This review aims to provide its readers a comprehensive overview of the possible mechanisms underlying the immunomodulatory effects exerted by stem/progenitor cell-derived EVs upon natural killer (NK) cells, dendritic cells (DCs), monocytes/macrophages, microglia, T cells, and B cells.

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“…Inflammatory priming induces the increase of miR-155 and miR-146 levels within MSC-EVs (Di Trapani et al, 2016). In particular, MSC-EVs induce the downregulation of PI3K/AKT signaling pathway components in B cells, inhibit B cell spreading, and reduce B cell viability via miR-155-5p (Adamo et al, 2019).…”

Section: Msc-evs and Adaptive Immune Systemmentioning

confidence: 99%

Extracellular Vesicle-Dependent Communication Between Mesenchymal Stromal Cells and Immune Effector Cells

Kamga

Tanasi

Krampera

2020

Front. Cell Dev. Biol.

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Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in the stromal tissues of the body and capable of promoting tissue repair and attenuating inflammatory processes through their immunomodulatory properties. Preclinical and clinical observations revealed that not only direct intercellular communication mediates MSC properties; in fact, a pivotal role is also played by the release of soluble and bioactive factors, such as cytokines, growth factor and extracellular vesicles (EVs). EVs are membrane-coated vesicles containing a large variety of bioactive molecules, including lipids, proteins, and nucleic acids, such as RNA. EVs release their contents into target cells, thus influencing cell fate through the control of intracellular processes. In addition, MSC-derived EVs can mediate modulatory effects toward different effector cells belonging to both innate and adaptive immunity. In this review, we will discuss the literature data concerning MSC-derived EVs, including the current standardized methods for their isolation and characterization, the mechanisms supporting their immunoregulatory properties, and their potential clinical application as alternative to MSC-based therapy for inflammatory reactions, such as graft-versus-host disease (GvHD).

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Extracellular Vesicles Mediate Mesenchymal Stromal Cell-Dependent Regulation of B Cell PI3K-AKT Signaling Pathway and Actin Cytoskeleton

Cited by 67 publications

References 96 publications

HS-5 and HS-27A Stromal Cell Lines to Study Bone Marrow Mesenchymal Stromal Cell-Mediated Support to Cancer Development

HS-5 and HS-27A Stromal Cell Lines to Study Bone Marrow Mesenchymal Stromal Cell-Mediated Support to Cancer Development

Immunoregulatory Effects of Stem Cell-Derived Extracellular Vesicles on Immune Cells

Extracellular Vesicle-Dependent Communication Between Mesenchymal Stromal Cells and Immune Effector Cells

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