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

2021 ◽  
Author(s):  
Ya Gao ◽  
Wei-Ru Li ◽  
Xiao-Yin Bu ◽  
Ying Xu ◽  
Sheng-Chun Cai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mouse Model ◽  
Humanized Mice ◽  
Control Group ◽  
Lymphocyte Infiltration ◽  
Effector Cells ◽  
T Effector Cells ◽  
Target Organs ◽  
Amniotic Mesenchymal Stem Cells

Abstract 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.

scholarly journals Human Amniotic Mesenchymal Stem Cells Inhibit aGVHD by Regulating Balance of Treg and T Effector Cells

2021 ◽  
Vol Volume 14 ◽  
pp. 3985-3999
Author(s):  
Ya Gao ◽  
Weiru Li ◽  
Xiaoyin Bu ◽  
Ying Xu ◽  
Shengchun Cai ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Effector Cells ◽  
T Effector Cells ◽  
Amniotic Mesenchymal Stem Cells

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

2021 ◽  
Author(s):  
Ya Gao ◽  
Weiru Li ◽  
Xiaoyin Bu ◽  
Ying Xu ◽  
Shengchun Cai ◽  
...  
Keyword(s):  
T Cells ◽  
Mouse Models ◽  
Treg Cells ◽  
Control Group ◽  
Lymphocyte Infiltration ◽  
Humanized Mouse ◽  
Effector Cells ◽  
T Effector Cells ◽  
Target Organs ◽  
Human T Cells

Abstract 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.

scholarly journals Intravenous Administration of Human Amniotic Mesenchymal Stem Cells in the Subacute Phase of Cerebral Infarction in a Mouse Model Ameliorates Neurological Disturbance by Suppressing Blood Brain Barrier Disruption and Apoptosis via Immunomodulation

2021 ◽  
Vol 30 ◽  
pp. 096368972110241
Author(s):  
Yasunori Yoshida ◽  
Toshinori Takagi ◽  
Yoji Kuramoto ◽  
Kotaro Tatebayashi ◽  
Manabu Shirakawa ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mouse Model ◽  
Cerebral Infarction ◽  
Blood Brain Barrier ◽  
Brain Infarction ◽  
Brain Barrier ◽  
Neurological Deficits ◽  
Immunomodulatory Effects ◽  
Amniotic Mesenchymal Stem Cells

Neuro-inflammation plays a key role in the pathophysiology of brain infarction. Cell therapy offers a novel therapeutic option due to its effect on immunomodulatory effects. Amniotic stem cells, in particular, show promise owing to their low immunogenicity, tumorigenicity, and easy availability from amniotic membranes discarded following birth. We have successfully isolated and expanded human amniotic mesenchymal stem cells (hAMSCs). Herein, we evaluated the therapeutic effect of hAMSCs on neurological deficits after brain infarction as well as their immunomodulatory effects in a mouse model in order to understand their mechanisms of action. One day after permanent occlusion of the middle cerebral artery (MCAO), hAMSCs were intravenously administered. RT-qPCR for TNFα, iNOS, MMP2, and MMP9, immunofluorescence staining for iNOS and CD11b/c, and a TUNEL assay were performed 8 days following MCAO. An Evans Blue assay and behavioral tests were performed 2 days and several months following MCAO, respectively. The results suggest that the neurological deficits caused by cerebral infarction are improved in dose-dependent manner by the administration of hAMSCs. The mechanism appears to be through a reduction in disruption of the blood brain barrier and apoptosis in the peri-infarct region through the suppression of pro-inflammatory cytokines and the M2-to-M1 phenotype shift.

scholarly journals Effects of icariin on the proliferation and osteogenic differentiation of human amniotic mesenchymal stem cells

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Fang Wang ◽  
Zhiyong Yang ◽  
Wei He ◽  
Qinggao Song ◽  
Kun Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Immunocytochemical Staining ◽  
Control Group ◽  
Engineering Technology ◽  
Alizarin Red ◽  
Human Amnion ◽  
Alp Activity ◽  
Amniotic Mesenchymal Stem Cells

Abstract Background Tissue engineering technology has been applied extensively for clinical research and human amnion mesenchymal stem cells (hAMSCs) could cause mesenchymal stem cells to differentiate into the bone tissue. However, it is necessary to develop and identify the safer appropriate amount of osteogenic inducer. The objective of this study is to investigate the effect of icariin (ICA) on the proliferation and osteogenic differentiation of hAMSCs. Methods The morphology and phenotype of hAMSCs were discovered by flow cytometry and immunocytochemical staining. The osteogenic differentiation of hAMSCs under the influence of different concentrations of ICA were assessed by alkaline phosphatase (ALP) activity substrate assay and alizarin red staining. Results MTT assay revealed that the hAMSCs pretreated with ICA exhibited increased proliferation when compared with the control group, and the most optimum concentration of ICA was 1 × 10− 6 mol/L. The combined analysis of ALP activity and ARS staining showed that ICA could significantly promote the osteogenic differentiation of hAMSCs, and the effect was most significant when the concentration of ICA was 1 × 10− 6 mol/L. Conclusion All the above results implied that ICA could significantly increase proliferation and enhance the osteogenic differentiation of hAMSCs, especially when the concentration of ICA was 1 × 10− 6 mol/L.

scholarly journals Effects of icariin on the proliferation and osteogenic differentiation of human amniotic mesenchymal stem cells

2020 ◽  
Author(s):  
Fang Wang ◽  
Zhiyong Yang ◽  
He Wei ◽  
Qinggao Gao ◽  
Kun Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Immunocytochemical Staining ◽  
Control Group ◽  
Engineering Technology ◽  
Alizarin Red ◽  
Human Amnion ◽  
Alp Activity ◽  
Amniotic Mesenchymal Stem Cells

Abstract Background Tissue engineering technology has been applied extensively for clinical research and human amnion mesenchymal stem cells (hAMSCs) could cause mesenchymal stem cells to differentiate into the bone tissue. However, it is necessary to develop and identify the safer appropriate amount of osteogenic inducer. The objective of this study is to investigate the effect of icariin (ICA) on the proliferation and osteogenic differentiation of hAMSCs. Methods The morphology and phenotype of hAMSCs were discovered by flow cytometry and immunocytochemical staining. The osteogenic differentiation of hAMSCs under the influence of different concentrations of ICA were assessed by Alkaline phosphatase (ALP) activity substrate assay and Alizarin red Staining. Results MTT assay revealed that the hAMSCs pretreated with ICA exhibited increased proliferation when compared with the control group, and the most optimum concentration of ICA was 1 × 10− 6 mol/L. The combined analysis of ALP activity and ARS staining showed that ICA could significantly promote the osteogenic differentiation of hAMSCs, and the effect was most significant when the concentration of ICA was 1 × 10− 6 mol/L. Conclusion All above results implied that ICA could significantly increase proliferation and enhanced the osteogenic differentiation of hAMSCs, especially when the concentration of ICA was 1 × 10− 6 mol/L.

Multiple systemic transplantations of human amniotic mesenchymal stem cells exert therapeutic effects in an ALS mouse model

2014 ◽  
Vol 357 (3) ◽  
pp. 571-582 ◽  
Author(s):  
Haitao Sun ◽  
Zongliu Hou ◽  
Huaqiang Yang ◽  
Mingyao Meng ◽  
Peng Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Mouse Model ◽  
Therapeutic Effects ◽  
Amniotic Mesenchymal Stem Cells

scholarly journals Effects of icariin on the proliferation and osteogenic differentiation of human amniotic mesenchymal stem cells

2020 ◽  
Author(s):  
Fang Wang ◽  
Zhiyong Yang ◽  
He Wei ◽  
Qinggao Gao ◽  
Kun Wang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Immunocytochemical Staining ◽  
Control Group ◽  
Engineering Technology ◽  
Alizarin Red ◽  
Human Amnion ◽  
Alp Activity ◽  
Amniotic Mesenchymal Stem Cells

Abstract Background: Tissue engineering technology has been applied extensively for clinical research and human amnion mesenchymal stem cells (hAMSCs) could cause mesenchymal stem cells to differentiate into the bone tissue. However, it is necessary to develop and identify the safer appropriate amount of osteogenic inducer. The objective of this study is to investigate the effect of icariin (ICA) on the proliferation and osteogenic differentiation of hAMSCs.Methods: The morphology and phenotype of hAMSCs were discovered by flow cytometry and immunocytochemical staining. The osteogenic differentiation of hAMSCs under the influence of different concentrations of ICA were assessed by Alkaline phosphatase (ALP) activity substrate assay and Alizarin red Staining.Results: MTT assay revealed that the hAMSCs pretreated with ICA exhibited increased proliferation when compared with the control group, and the most optimum concentration of ICA was 1×10-6 mol/L. The combined analysis of ALP activity and ARS staining showed that ICA could significantly promote the osteogenic differentiation of hAMSCs, and the effect was most significant when the concentration of ICA was 1×10-6mol/L.Conclusion: All above results implied that ICA could significantly increase proliferation and enhanced the osteogenic differentiation of hAMSCs, especially when the concentration of ICA was 1×10-6 mol/L.Keywords: Human amniotic mesenchymal stem cell, Icariin, Proliferation, Osteogenic differentiation

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