Characterization and immunogenicity of bone marrow-derived mesenchymal stem cells under osteoporotic conditions

Huang, Yingkang; Yin, Yin; Gu, Yanzheng; Gu, Qianqun; Yang, Huilin; Zhou, Zhengyu; Shi, Qin

doi:10.1007/s11427-019-1555-9

Cited by 45 publications

(35 citation statements)

References 57 publications

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“…During antigen presentation, mDCs gradually mature and express high levels of the costimulatory molecules CD80 and CD86 [20]. CTLs are activated through the combination of mDCs and numerous cellular signals, which initi-ates an immune response.…”

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confidence: 99%

Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia

Zheng

Liu

Shao

et al. 2020

Mediators of Inflammation

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This study is aimed at investigating the effects of shikonin, a pyruvate kinase M2 (PKM2) inhibitor, on the functions of myeloid dendritic cells (mDCs) in a mouse model of severe aplastic anemia (AA) generated by total body irradiation and lymphocyte infusion. Flow cytometry and qPCR were used to determine the proportions of PKM2+ mDCs and other immune indicators in the AA mice. Glucose consumption level, pyruvate generation level, and ATP content were used to determine the level of glycolytic metabolism in the mDCs. The survival rates of AA mice were evaluated after the administration of shikonin or the immunosuppressive agent cyclosporin A. The AA mice displayed pancytopenia, decreased CD4+/CD8+ cell ratio, increased perforin and granzyme levels in CD8+ cells, increased costimulatory CD80 and CD86 expressions, and inadequate regulatory T cell number. In vivo animal experiments showed that the shikonin-mediated inhibition of the PKM2 expression in mice was associated with high survival rates. In addition, the administration of cyclosporin A or shikonin decreased the expression of cytotoxic molecules and costimulatory CD80 and CD86 on CD8+ cells. Taken together, the results of this study indicated that shikonin could inhibit the activation and proliferation of mDCs as well as the activation of downstream cytotoxic T cells by reducing the PKM2 level in mDCs.

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confidence: 99%

Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia

Zheng

Liu

Shao

et al. 2020

Mediators of Inflammation

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“…Different from BMSC, MSCs isolated from placenta exhibit greater proliferative and differentiative potentials than BMSCs, most likely because of the early embryologic origin of amniotic membrane (AM-) and placenta (PL-) MSCs as compared with BMMSCs [24,25]. hAMSCs have intermediate levels of HLA major histocompatibility complex (MHC) class I molecules, but do not have HLA class II antigens, FAS ligand, and the costimulatory molecules, therefore, do not activate alloreactive T cells [26,27,28]. Our results indicated that hAMSCs showed broblast-shaped morphology and adherence to plastic, the cell-surface markers of more than 90% of the hAMSCs were positive for CD90, CD105 and CD73 while negative for CD45, CD11b, HLA-DR and CD34.…”

Section: Discussionmentioning

confidence: 99%

“…NPG mice received 200 cGy irradiation before 3×10 6 human PBMC injected from tail vein died within 12 to 14 days after cell transfer. In contrast, those NPG mice only received human PBMC survived for 28 To investigate the effect of hAMSCs on T effector cells and Treg cells, target organs of mice were grinding and analyzed by ow cytometry. We found that the proportion of CD3+/CD4 + T cells of liver, spleen, lung and gut in mice receiving hAMSCs treatment were signi cantly lower than those untreated hAMSCs control aGVHD by decreasing in ammatory cytokine secretion in target organs hAMSCs treatment signi cantly inhibited the secretion of human in ammatory cytokines, like IL-17A, IFNγ, TNF and IL-2 from the lung, liver, gut or blood on day 3 after transplantation.…”

Section: A Human Xenogeneic Acute Gvhd Model Was Successfully Establimentioning

confidence: 99%

Human Amniotic Mesenchymal Stem Cells Inhibit aGVHD in Humanized NPG Mice by Regulating Balance of Treg Versus T Effector Cells

Gao

et al. 2021

Preprint

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Background: Acute graft versus host disease(aGVHD) occurs when immunocompetent T cells in the donated tissue recognize the recipient as foreign after allo-HSCT, which can severely affect quality of life. Although previous studies indicated that MSC may be a salvage therapeutic agent for aGVHD, the mechanism is not yet fully clear. The aim of this study was to explore the therapeutic efficacy and underlying mechanisms of hAMSCs transplantation for humanized aGVHD mouse model.Methods: We established a novel xenogeneic (xeno)-aGVHD humanized mouse models by transplanting purified human T cells from peripheral blood into immunodeficient NOD-PrkdcscidIl2rγnull (NPG) mouse. In those mouse models, lymphocyte infiltration of target organs was detected by HE staining method and immunohistochemistry respectively. The biological characteristics of hAMSCs were investigated. hAMSCs labeled with GFP were administered to NPG mice to explore the homing ability of hAMSCs. Mice are divided into normal(control) group, aGVHD group and hAMSCs treatment group. After 3 days of injection of PBMC, hAMSCs and PBS were given into the different groups. T effector and Treg cells levels of each group in target organs were detected by flow cytometry and cytometric bead array (CBA).Results: We successfully established xenogeneic aGVHD “humanized model” by using NOD-PrkdcscidIl2rγnull (NPG) mice, which showed lymphocytes infiltration in the liver, spleen and lung. hAMSCs therapy improved systemic inflammation and inhibited aGVHD in humanized mouse through reduced villous blunting and lymphocyte infiltration into the lamina propria of the gut while reducing vascular endothelialitis and lymphocyte infiltration into the parenchyma of the liver and lung. In addition, hAMSCs suppresses xenogenesis CD3+/CD4+ and CD3+/CD8+ T cell concentration and increases the proportion of Treg cells. Our data also show that hAMSC can reduce the level of IL-17A, INF-γ, TNF and IL-2 that involved in the pathogenesis of aGVHD target organs.Conclusions: NPG murine environment is capable of activating human T cells to produce aGVHD pathology to mimic aGVHD in humans. hAMSCs controlled aGVHD by decreasing inflammatory cytokine secretion within target organs through modulating balance of Treg versus T effector cells in humanized mice.

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“…Different from BM-MSCs, MSCs isolated from placenta exhibit greater proliferative and differentiation potential than BM-MSCs, most likely because of the early embryologic origin of amniotic membrane and placenta MSCs compared with BMMSCs [23,24]. The hAMSCs have intermediate levels of HLA MHC class I molecules, but do not have HLA class II antigens, FAS ligand, and the co-stimulatory molecules, and therefore, do not activate alloreactive T cells [25,26,27]. The hAMSCs exhibited a broblast-shaped morphology and adherence to plastic, our data show that the cell-surface markers of the hAMSCs were positive for CD90, CD73 and CD105 while negative for CD45, CD11b, HLA-DR and CD34.…”

Section: Discussionmentioning

confidence: 99%

Human Amniotic Mesenchymal Stem Cells Inhibit aGVHD in Humanized Mice by Regulating the Balance of Treg and T Effector Cells

Gao

et al. 2021

Preprint

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Background: Acute graft versus host disease (aGVHD) remains a leading cause of transplant-related mortality following allogeneic haematopoietic cell transplantation(allo-HCT). Although previous studies indicated that mesenchymal stem cells (MSCs) may be a salvage therapeutic agent for aGVHD, the mechanism is not yet fully clear. Human amniotic mesenchymal stem cells (hAMSCs) is a novel MSCs, compared with bone marrow mesenchymal stem cells, it has the advantage of being non-invasive, and also has stronger proliferation ability than that of BM-MSCs and equivalent immune regulation ability as BM-MSCs. The aim of this study was to explore the therapeutic efficacy and underlying mechanisms of human amniotic mesenchymal stem cells transplantation for the humanized aGVHD mouse model.Methods: We established a humanized aGVHD mouse model by transplanting human peripheral blood mononuclear cells (PBMCs) into NOD-PrkdcscidIL2rγnull (NPG) mice, hAMSCs collected from discarded placenta of healthy pregnant women after delivery. Mice were divided into control group (untreated), aGVHD group, and hAMSCs treatment group, the hAMSCs labeled with GFP were administered to aGVHD mice to explore the homing ability of hAMSCs. T effector and Treg cell levels and cytokines of each group in target organs were detected by flow cytometry and cytometric bead array (CBA) respectively.Results: We successfully established a humanized aGVHD mouse model using NPG mice. The hAMSCs have the ability to inhibit aGVHD in this mouse model through reduced villous blunting and lymphocyte infiltration into the lamina propria of the gut while reducing vascular endothelialitis and lymphocyte infiltration into the parenchyma of the liver and lung. hAMSCs suppressed xenogenesis CD3+CD4+ T and CD3+CD8+ T cell expression and increased the proportion of Treg cells, and besides, hAMSCs can reduce the levels of IL-17A, INF-γ, TNF, and IL-2 in aGVHD target organs.Conclusions: The NPG murine environment was capable of activating human T cells to produce aGVHD pathology to mimic aGVHD as in humans. The hAMSCs controlled aGVHD by decreasing inflammatory cytokine secretion within target organs by modulating the balance of Treg and T effector cells in humanized mice.

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Characterization and immunogenicity of bone marrow-derived mesenchymal stem cells under osteoporotic conditions

Cited by 45 publications

References 57 publications

Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia

Effects of Shikonin on the Functions of Myeloid Dendritic Cells in a Mouse Model of Severe Aplastic Anemia

Human Amniotic Mesenchymal Stem Cells Inhibit aGVHD in Humanized NPG Mice by Regulating Balance of Treg Versus T Effector Cells

Human Amniotic Mesenchymal Stem Cells Inhibit aGVHD in Humanized Mice by Regulating the Balance of Treg and T Effector Cells

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