Human amnion-derived mesenchymal stem cells attenuate xenogeneic graft-versus-host disease by preventing T cell activation and proliferation

Tago, Yoshiyuki; Kobayashi, Chiho; Ogura, Mineko; Wada, Jutaro; Yamaguchi, Sho; Yamaguchi, Takashi; Hayashi, Masahiro; Nakaishi, Tomoyuki; Kubo, Hiroshi; Ueda, Yoshiyasu

doi:10.1038/s41598-021-81916-y

Cited by 14 publications

(11 citation statements)

References 42 publications

(41 reference statements)

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“…They also compared the immunomodulatory effects of AMSCs and BM-MSCs in vitro, and found that both AMSCs and BM-MSCs reduced the concentration of TNF-α and IFN-γ expressed by PBMCs. 48 However, this study did not detect T cell and inflammatory cytokine levels in the target organs of aGVHD mice. We examined CD3+CD4+ T and CD3+CD8+ T cells in the main target organs of our aGVHD mice, and found a significant decrease in the proportion of CD3+CD4+ T and CD3+CD8+ T cells in these tissues of mice treated with hAMSCs compared to control group.…”

Section: Discussioncontrasting

confidence: 59%

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

Gao¹,

Li²,

Bu³

et al. 2021

JIR

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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). Human amniotic mesenchymal stem cells (hAMSCs) are a novel mesenchymal stem cells (MSCs), which have stronger proliferation and immunomodulatory ability compared with bone marrow mesenchymal stem cells (BM-MSCs). Besides, as the amniotic membrane is often treated as medical waste after delivery, hAMSCs can be obtained conveniently and noninvasively. The aim of this study was to explore the therapeutic efficacy and underlying mechanisms of hAMSCs 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-Prkdc scid IL2rγ null (NPG) mice, human amniotic membrane collected from discarded placenta of healthy pregnant women after delivery and hAMSCs were extracted from amniotic membrane and expanded in vitro. Mice were divided into untreated group (Control), aGVHD group (aGVHD), and hAMSCs treatment group (aGVHD+hAMSCs), the hAMSCs labeled with GFP were administered to aGVHD mice to explore the homing ability of hAMSCs. T effector and regulatory T cells (Tregs) 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 of the gut while reducing inflammatory edema, tissue destruction and lymphocyte infiltration into the parenchyma of the liver and lung. hAMSCs suppressed CD3+CD4+ T and CD3+CD8+ T cell expression and increased the proportion of Tregs, and besides, hAMSCs can reduce the levels of IL-17A, INF-γ, and TNF in aGVHD target organs. Conclusion 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 Tregs and T effector cells in humanized mice.

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Section: Discussioncontrasting

confidence: 59%

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

Gao¹,

Li²,

Bu³

et al. 2021

JIR

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“…Solid black arrows indicate GvHD pathology, including high infiltration of mononuclear cells in hepatic and lung tissues, shortening and/or structural abnormality of intestinal villi, and bronchial luminal narrowing. [55][56][57][58][59] The corresponding number at each scale bar indicates an image size (mm). was demonstrated in a previous study, 68 suggesting the feasibility of this approach.…”

Section: Discussionmentioning

confidence: 99%

“…(D) Histopathology of intestine, liver, and lung tissues obtained from all groups. Solid black arrows indicate GvHD pathology, including high infiltration of mononuclear cells in hepatic and lung tissues, shortening and/or structural abnormality of intestinal villi, and bronchial luminal narrowing [55][56][57][58][59]. The corresponding number at each scale bar indicates an image size (mm).…”

mentioning

confidence: 99%

Universal allogeneic CAR T cells engineered with Sleeping Beauty transposons and CRISPR-CAS9 for cancer immunotherapy

Tipanee¹,

Samara-Kuko²,

Gevaert³

et al. 2022

Molecular Therapy

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“…A recent study showed that AMSCs reduced the activity of human CD8 + T cells and TNF-α in the peripheral blood of xeno-GVHD mice. They also compared the immunomodulatory effects of AMSCs and BM-MSCs in vitro, and found that both AMSCs and BM-MSCs reduced the concentration of TNF-α and IFN-γ expressed by PBMCs [35]. However, this study did not detect T cell and in ammatory cytokine levels in the target organs of aGVHD mice.…”

Section: Discussionmentioning

confidence: 73%

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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Human amnion-derived mesenchymal stem cells attenuate xenogeneic graft-versus-host disease by preventing T cell activation and proliferation

Cited by 14 publications

References 42 publications

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

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

Universal allogeneic CAR T cells engineered with Sleeping Beauty transposons and CRISPR-CAS9 for cancer immunotherapy

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

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