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

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Human Gingiva-Derived Mesenchymal Stem Cells Ameliorate Streptozoticin-induced T1DM in mice via Suppression of T effector cells and Up-regulating Treg Subsets

Scientific Reports ◽

10.1038/s41598-017-14979-5 ◽

2017 ◽

Vol 7 (1) ◽

Cited By ~ 14

Author(s):

Wei Zhang ◽

Li Zhou ◽

Junlong Dang ◽

Ximei Zhang ◽

Julie Wang ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Effector Cells ◽

T Effector Cells ◽

Human Gingiva

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Human amniotic mesenchymal stem cells to promote/suppress cancer: two sides of the same coin

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02196-x ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Ameneh Jafari ◽

Mostafa Rezaei-Tavirani ◽

Behrouz Farhadihosseinabadi ◽

Hakimeh Zali ◽

Hassan Niknejad

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Cancer Treatment ◽

Cancer Progression ◽

Adult Stem Cells ◽

Treatment Modalities ◽

Human Amniotic Membrane ◽

Amniotic Mesenchymal Stem Cells ◽

Growth And Aging

AbstractCancer is a leading cause of death in both developed and developing countries, and because of population growth and aging, it is a growing medical burden worldwide. With robust development in medicine, the use of stem cells has opened new treatment modalities in cancer therapy. In adult stem cells, mesenchymal stem cells (MSCs) are showing rising promise in cancer treatment due to their unique properties. Among different sources of MSCs, human amniotic fluid/membrane is an attractive and suitable reservoir. There are conflicting opinions about the role of human amniotic membrane/fluid mesenchymal stem cells (hAMSCS/hAFMSCs) in cancer, as some studies demonstrating the anticancer effects of these cells and others suggesting their progressive effects on cancer. This review focuses on recent findings about the role of hAMSCs/hAFMSCs in cancer treatment and summarizes the suppressing as well as promoting effects of these cells on cancer progression and underling mechanisms.

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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

Cell Transplantation ◽

10.1177/09636897211024183 ◽

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.

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miR-138/miR-222 Overexpression Characterizes the miRNome of Amniotic Mesenchymal Stem Cells in Obesity

Stem Cells and Development ◽

10.1089/scd.2016.0127 ◽

2017 ◽

Vol 26 (1) ◽

pp. 4-14 ◽

Cited By ~ 9

Author(s):

Carmela Nardelli ◽

Ilaria Granata ◽

Laura Iaffaldano ◽

Valeria D'Argenio ◽

Valentina Del Monaco ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Amniotic Mesenchymal Stem Cells

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Osteogenic differentiation of human amniotic mesenchymal stem cells in chitosan-carbonate apatite scaffold (in vivo study)

Contemporary Clinical Dentistry ◽

10.4103/ccd.ccd_627_18 ◽

2018 ◽

Vol 9 (4) ◽

pp. 592

Author(s):

MichaelJosef Kridanto Kamadjaja ◽

Sherman Salim ◽

FedikAbdul Rantam ◽

Ni PutuMira Sumarta

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

In Vivo Study ◽

Carbonate Apatite ◽

Amniotic Mesenchymal Stem Cells

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Effects of Interferon-γ on Proliferation and Ability of Secretion of Human Amniotic Mesenchymal Stem Cells

Blood ◽

10.1182/blood-2019-125500 ◽

2019 ◽

Vol 134 (Supplement_1) ◽

pp. 5012-5012

Author(s):

Ya Gao ◽

Ying Xu ◽

Weiru Li ◽

Yintian Zhang ◽

Baohong Ping ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Conflicts Of Interest ◽

Interferon Γ ◽

Cell Counting ◽

Inflammatory Factors ◽

Complete Medium ◽

Amniotic Mesenchymal Stem Cells ◽

Soluble Hla ◽

Ifn Γ

Objective:The immunoregulatory properties and proliferation of mesenchymal stem cells (MSCs) could be affected by inflammatory factors. However, there have been few studies about human amniotic MSCs (hAMSCs). We investigated the effects of interferon (IFN)-γ on the proliferation and apoptosis of hAMSCs, and measured the level of inflammatory factors secreted by hAMSCs. Result:hAMSCs were cultured with complete medium with different concentrations of IFN-γ. We detected the proliferation of hAMSCs by Cell Counting Kit-8 assays, analysed apoptosis by flow cytometry (FCM) at 48 h, and mesasured the level of inflammatory factors such as solube HLA-G and prostaglandin E2 (PGE2) in the supernatant at 48 h by ELISA. The level of kynurenine (KYN) was measured by ultraviolet spectrophotometry. As culture time increased, the proliferation of hAMSCs with different concentrations of IFN-γ increased rapidly from day 1 to day 4, and then the growth rate slowed. FCM indicated that there was no significant apoptosis in the 100 ng/ml IFN-γ group compared with cells without IFN-γ. The level of PGE2 and soluble HLA-G in cells with IFN-γ was higher compared with those without IFN-γ. The level of KYN increased significantly in the cells with IFN-γ. Conclusion:IFN-γ did not affect the growth and proliferation of hAMSCs, and promoted secretion of PGE2 and soluble HLA-G, and enhanced activity of indoleamine 2,3-dioxygenase (IDO), providing a theoretical basis for hAMSCs to prevent and treat graft-versus-host disease. Disclosures No relevant conflicts of interest to declare.

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