Human Amniotic Mesenchymal Stem Cells Promote Endogenous Bone Regeneration

Jin, Li; Zhou, Zixiang; Wen, Ji; Jiang, Fei; Xia, Yang

doi:10.3389/fendo.2020.543623

Cited by 15 publications

(13 citation statements)

References 121 publications

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“… 19 Meanwhile, the amniotic membrane is an avascular structure only composed of epithelium and mesenchyme, which makes it easy to remove epithelial layer by Dispase II and thus obtain hAMSCs without contamination of endothelial cells and hematopoietic cells. 20 Our previous study found that the immunomodulatory and proliferation activity of hAMSCs is higher than that of human bone marrow MSCs in vitro. 21 , 22 Yamahara et al confirmed that human amnion-derived MSCs had immunomodulatory activity equal to or higher than that of human bone marrow MSCs.…”

Section: Introductionmentioning

confidence: 96%

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: Introductionmentioning

confidence: 96%

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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“…The amniotic membrane is a “discarded” tissue of particular interesting after parturition, which contains epithelial and mesenchymal stem cells with low immunogenicity, robust proliferation, multi-lineage differentiation capacity, and easy procurement [ 37 – 39 ]. Therefore, hAMSC-based therapy has been widely explored to promote endogenous regeneration and alleviate the untoward effect of traditional treatment [ 40 ]. To date, hAMSCs have been reported as appropriate sources with therapeutic effects in regenerative medicine and tissue engineering such as premature ovarian insufficiency (POI) [ 41 ], premature ovarian failure (POF) [ 36 ], wound healing and epithelialization [ 42 ], hepatocellular carcinoma [ 43 ], and endogenous bone regeneration [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, hAMSC-based therapy has been widely explored to promote endogenous regeneration and alleviate the untoward effect of traditional treatment [ 40 ]. To date, hAMSCs have been reported as appropriate sources with therapeutic effects in regenerative medicine and tissue engineering such as premature ovarian insufficiency (POI) [ 41 ], premature ovarian failure (POF) [ 36 ], wound healing and epithelialization [ 42 ], hepatocellular carcinoma [ 43 ], and endogenous bone regeneration [ 40 ]. Generally, hAMSCs function via direct- and trans-differentiation, paracrine, and autocrine (e.g., extracellular proteins, anti-bacterial peptides, growth factors, angio-modulatory cytokines, bioactive factors), immunoregulation (e.g., anti-inflammatory agents, polarization of T lymphocytes, or macrophages), activating endogenous regeneration and serving as constitutive microenvironment [ 17 , 39 – 41 ].…”

Section: Discussionmentioning

confidence: 99%

Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions

Sun

Wang

et al. 2022

Stem Cell Res Ther

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Background Human amniotic mesenchymal stem cells (hAMSCs) are splendid cell sources for clinical application in the administration of numerous refractory and relapse diseases. Despite the preferable prospect of serum-free (SF) condition for cell product standardization and pathogenic contamination remission, yet the systematic and detailed impact upon hAMSCs at both cellular and transcriptomic levels is largely obscure. Methods For the purpose, we preconditioned hAMSCs under serum-containing (SC) and SF medium for 48 h and compared the biological signatures and biofunctions from the view of cell morphology, immunophenotypes, multi-lineage differentiation in vitro, cell vitality, cytokine expression, and immunosuppressive effect upon the subpopulations of T lymphocytes, together with the PI3K-AKT-mTOR signaling reactivation upon cell vitality. Meanwhile, we took advantage of RNA-SEQ and bioinformatic analyses to verify the gene expression profiling and genetic variation spectrum in the indicated hAMSCs. Results Compared with those maintained in SC medium, hAMSCs pretreated in SF conditions manifested conservation in cell morphology, immunophenotypes, adipogenic differentiation, and immunosuppressive effect upon the proliferation and activation of most of the T cell subpopulations, but with evaluated cytokine expression (e.g., TGF-β1, IDO1, NOS2) and declined osteogenic differentiation and cell proliferation as well as proapoptotic and apoptotic cells. The declined proliferation in the SF group was efficiently rescued by PI3K-AKT-mTOR signaling reactivation. Notably, hAMSCs cultured in SF and SC conditions revealed similarities in gene expression profiling and variations in genetic mutation at the transcriptome level. Instead, based on the differentially expressed genes and variable shear event analyses, we found those genes were mainly involved in DNA synthesis-, protein metabolism-, and cell vitality-associated biological processes and signaling pathways (e.g., P53, KRAS, PI3K-Akt-mTOR). Conclusions Collectively, our data revealed the multifaceted cellular and molecular properties of hAMSCs under SC and SF conditions, which suggested the feasibility of serum-free culture for the preferable preparation of standardized cell products for hAMSC drug development and clinical application.

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“…These bodies of literature suggest that AECs and AFCs have the potential to effectively treat a variety of conditions, ranging from cutaneous wounds to orthopedic conditions, to liver or lung disorders, and neurological conditions. While some efficacy has been shown in certain clinical contexts [ 59 , 60 , 61 ], it is clear that these treatments are safe when properly administered [ 62 , 63 ]. Furthermore, the therapeutic effects appear to be mediated not necessarily by the cells directly, but by their secreted trophic factors [ 64 , 65 , 66 , 67 , 68 ].…”

Section: Introductionmentioning

confidence: 99%

Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation

et al. 2022

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Myofibroblast activation is a cellular response elicited by a variety of physiological or pathological insults whereby cells initiate a coordinated response intended to eradicate the insult and then revert back to a basal state. However, an underlying theme in various disease states is persistent myofibroblast activation that fails to resolve. Based on multiple observations, we hypothesized that the secreted factors harvested from co-culturing amniotic stem cells might mimic the anti-inflammatory state that cell-free amniotic fluid (AF) elicits. We optimized an amnion epithelial and amniotic fluid cell co-culture system, and tested this hypothesis in the context of myofibroblast activation. However, we discovered that co-cultured amniotic cell conditioned media (coACCM) and AF have opposing effects on myofibroblast activation: coACCM activates the epithelial–mesenchymal transition (EMT) and stimulates gene expression patterns associated with myofibroblast activation, while AF does the opposite. Intriguingly, extracellular vesicles (EVs) purified from AF are necessary and sufficient to activate EMT and inflammatory gene expression patterns, while the EV-depleted AF potently represses these responses. In summary, these data indicate that coACCM stimulates myofibroblast activation, while AF represses it. We interpret these findings to suggest that coACCM, AF, and fractionated AF represent unique biologics that elicit different cellular responses that are correlated with a wide variety of pathological states, and therefore could have broad utility in the clinic and the lab.

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Human Amniotic Mesenchymal Stem Cells Promote Endogenous Bone Regeneration

Cited by 15 publications

References 121 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

Systematic comparation of the biological and transcriptomic landscapes of human amniotic mesenchymal stem cells under serum-containing and serum-free conditions

Comparative Analysis of Co-Cultured Amniotic Cell-Conditioned Media with Cell-Free Amniotic Fluid Reveals Differential Effects on Epithelial–Mesenchymal Transition and Myofibroblast Activation

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