Amniotic mesenchymal cells from pre‐eclamptic placentae maintain immunomodulatory features as healthy controls

Pianta, Stefano; Magatti, Marta; Vertua, Elsa; Signoroni, Patrizia Bonassi; Muradore, Ivan; Nuzzo, Anna Maria; Rolfo, Alessandro; Silini, Antonietta; Quaglia, Federico; Todros, Tullia; Parolini, Ornella

doi:10.1111/jcmm.12715

Cited by 41 publications

(52 citation statements)

References 62 publications

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“…Higher expression of PD-L2 is observed in human amniotic mesenchymal stromal cells (hAMSCs) from preeclampsia patients than in hAMSCs from normal pregnant women, but conversely, these cells participate in offsetting the inflammatory environment that characterizes preeclampsia. In vitro experiments have shown that elevated PD-L2 levels in hAMSCs are associated with inhibition of CD4 + /CD8 + T-cell proliferation by suppressing Th1/Th2/Th17 polarization, inducing Tregs, blocking DCs, and switching M1 to M2 differentiation (66). To summarize, B7-DC is expressed on multiple cells and fluctuates during different pregnancy phases.…”

Section: B7-h1 and B7-dcmentioning

confidence: 99%

The Role of B7 Family Molecules in Maternal–Fetal Immunity

2020

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Pregnancy is a complex but well-arranged process, and a healthy fetus requires immune privilege and surveillance in the presence of paternally derived antigens. Maternal and fetal cells interact at the maternal-fetal interface. The upregulation and downregulation of maternal immunity executed by the leukocyte population predominantly depend on the activity of decidual natural killer cells and trophoblasts and are further modulated by a series of duplex signals. The B7 family, which consists of B7-1, B7-2, B7-H1, B7-DC, B7-H2, B7-H3, B7-H4, B7-H5, BTNL2, B7-H6, and B7-H7, is one of the most characterized and widely distributed signaling molecule superfamilies and conducts both stimulatory and inhibitory signals through separate interactions. In particular, the roles of B7-1, B7-2, B7-H1, and their corresponding receptors in the progression of normal pregnancy and some pregnancy complications have been extensively studied. Together with the TCR-MHC complex, B7 and its receptors play a critical role in cell proliferation and cytokine secretion. Depending on this ligand-receptor crosstalk, the balance between the tolerance and rejection of the fetus is perfectly maintained. This review aims to provide an overview of the current knowledge of the B7 family and its functions in regulating maternal-fetal immunity through individual interactions.

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Section: B7-h1 and B7-dcmentioning

confidence: 99%

The Role of B7 Family Molecules in Maternal–Fetal Immunity

2020

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“…14 Amniotic cells and their secreted factors possess in vitro and in vivo immune-modulatory properties. They inhibit T-cell proliferation, [15][16][17][18] reduce the production of proinflammatory cytokines, 6,7,18,19 block the differentiation/maturation of monocytes into dendritic cells, [20][21][22] promote macrophage polarization toward an M2 anti-inflammatory phenotype, 8,23,24 induce regulatory T cells, 18,25,26 and reduce natural killer cytotoxicity. 27 However, to the best of our knowledge, no studies investigated the crosstalk between hAMSCs and immune cell populations that are involved in bleomycin-induced lung injury.…”

Section: Introductionmentioning

confidence: 99%

Amniotic MSCs reduce pulmonary fibrosis by hampering lung B-cell recruitment, retention, and maturation

Cargnoni

Romele

Signoroni

et al. 2020

Stem Cells Translational Medicine

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Growing evidence suggests a mechanistic link between inflammation and the development and progression of fibrotic processes. Mesenchymal stromal cells derived from the human amniotic membrane (hAMSCs), which display marked immunomodulatory properties, have been shown to reduce bleomycin‐induced lung fibrosis in mice, possibly by creating a microenvironment able to limit the evolution of chronic inflammation to fibrosis. However, the ability of hAMSCs to modulate immune cells involved in bleomycin‐induced pulmonary inflammation has yet to be elucidated. Herein, we conducted a longitudinal study of the effects of hAMSCs on alveolar and lung immune cell populations upon bleomycin challenge. Immune cells collected through bronchoalveolar lavage were examined by flow cytometry, and lung tissues were used to study gene expression of markers associated with different immune cell types. We observed that hAMSCs increased lung expression of T regulatory cell marker Foxp3, increased macrophage polarization toward an anti‐inflammatory phenotype (M2), and reduced the antigen‐presentation potential of macrophages and dendritic cells. For the first time, we demonstrate that hAMSCs markedly reduce pulmonary B‐cell recruitment, retention, and maturation, and counteract the formation and expansion of intrapulmonary lymphoid aggregates. Thus, hAMSCs may hamper the self‐maintaining inflammatory condition promoted by B cells that continuously act as antigen presenting cells for proximal T lymphocytes in injured lungs. By modulating B‐cell response, hAMSCs may contribute to blunting of the chronicization of lung inflammatory processes with a consequent reduction of the progression of the fibrotic lesion.

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“…Due to these features, in different preclinical inflammatory disease models, hAMSCs and their conditioned medium (CM-hAMSC) have been successfully exploited, including for lung [11][12][13][14] and liver fibrosis [15], wound healing [16][17][18], collagen-induced arthritis [19,20], multiple sclerosis [19], inflammatory bowel disease, colitis [21], sepsis [19], traumatic brain injury [22], and Huntington's disease [23]. Accordingly, in vitro, we and others have demonstrated that hAMSCs and CM-hAMSC suppress the proliferation, inflammatory cytokine production, and functions of T lymphocytes [24,25], monocytes [18], dendritic cells [26], macrophages [18], and natural killer cells [27], while inducing a phenotype and functional switch of monocytes toward macrophages with anti-inflammatory pro-regenerative M2-like features [18,25], supporting the expansions of regulatory T cells [24,25].…”

Section: Introductionmentioning

confidence: 99%

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

et al. 2020

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Human amniotic membrane and amniotic membrane-derived mesenchymal stromal cells (hAMSCs) have produced promising results in regenerative medicine, especially for the treatment of inflammatory-based diseases and for different injuries including those in the orthopedic field such as tendon disorders. hAMSCs have been proposed to exert their anti-inflammatory and healing potential via secreted factors, both free and conveyed within extracellular vesicles (EVs). In particular, EV miRNAs are considered privileged players due to their impact on target cells and tissues, and their future use as therapeutic molecules is being intensely investigated. In this view, EV-miRNA quantification in either research or future clinical products has emerged as a crucial paradigm, although, to date, largely unsolved due to lack of reliable reference genes (RGs). In this study, a panel of thirteen putative miRNA RGs (let-7a-5p, miR-16-5p, miR-22-5p, miR-23a-3p, miR-26a-5p, miR-29a-5p, miR-101-3p, miR-103a-3p, miR-221-3p, miR-423-5p, miR-425-5p, miR-660-5p and U6 snRNA) that were identified in different EV types was assessed in hAMSC-EVs. A validated experimental pipeline was followed, sifting the output of four largely accepted algorithms for RG prediction (geNorm, NormFinder, BestKeeper and ΔCt method). Out of nine RGs constitutively expressed across all EV isolates, miR-101-3p and miR-22-5p resulted in the most stable RGs, whereas miR-423-5p and U6 snRNA performed poorly. miR-22-5p was also previously reported to be a reliable RG in adipose-derived MSC-EVs, suggesting its suitability across samples isolated from different MSC types. Further, to shed light on the impact of incorrect RG choice, the level of five tendon-related miRNAs (miR-29a-3p, miR-135a-5p, miR-146a-5p, miR-337-3p, let-7d-5p) was compared among hAMSC-EVs isolates. The use of miR-423-5p and U6 snRNA did not allow a correct quantification of miRNA incorporation in EVs, leading to less accurate fingerprinting and, if used for potency prediction, misleading indication of the most appropriate clinical batch. These results emphasize the crucial importance of RG choice for EV-miRNAs in hAMSCs studies and contribute to the identification of reliable RGs such as miR-101-3p and miR-22-5p to be validated in other MSC-EVs related fields.

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Amniotic mesenchymal cells from pre‐eclamptic placentae maintain immunomodulatory features as healthy controls

Cited by 41 publications

References 62 publications

The Role of B7 Family Molecules in Maternal–Fetal Immunity

The Role of B7 Family Molecules in Maternal–Fetal Immunity

Amniotic MSCs reduce pulmonary fibrosis by hampering lung B-cell recruitment, retention, and maturation

miRNA Reference Genes in Extracellular Vesicles Released from Amniotic Membrane-Derived Mesenchymal Stromal Cells

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