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

Blood ◽  
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.

scholarly journals Interferon-γ enhances the therapeutic effect of mesenchymal stem cells on experimental renal fibrosis

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Ryo Kanai ◽  
Ayumu Nakashima ◽  
Shigehiro Doi ◽  
Tomoe Kimura ◽  
Ken Yoshida ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Prostaglandin E2 ◽  
Conditioned Medium ◽  
Renal Fibrosis ◽  
Interferon Γ ◽  
Prostaglandin E ◽  
Therapeutic Effects ◽  
Control Mscs ◽  
Ifn Γ

AbstractMesenchymal stem cells (MSCs) administered for therapeutic purposes can be activated by interferon-γ (IFN-γ) secreted from natural killer cells in injured tissues and exert anti-inflammatory effects. These processes require a substantial period of time, leading to a delayed onset of MSCs’ therapeutic effects. In this study, we investigated whether pretreatment with IFN-γ could potentiate the anti-fibrotic ability of MSCs in rats with ischemia–reperfusion injury (IRI) and unilateral ureter obstruction. Administration of MSCs treated with IFN-γ strongly reduced infiltration of inflammatory cells and ameliorated interstitial fibrosis compared with control MSCs without IFN-γ treatment. In addition, conditioned medium obtained from IFN-γ-treated MSCs decreased fibrotic changes in cultured cells induced by transforming growth factor-β1 more efficiently than that from control MSCs. Most notably, secretion of prostaglandin E2 from MSCs was significantly increased by treatment with IFN-γ. Increased prostaglandin E2 in conditioned medium obtained from IFN-γ-treated MSCs induced polarization of immunosuppressive CD163 and CD206-positive macrophages. In addition, knockdown of prostaglandin E synthase weakened the anti-fibrotic effects of MSCs treated with IFN-γ in IRI rats, suggesting the involvement of prostaglandin E2 in the beneficial effects of IFN-γ. Administration of MSCs treated with IFN-γ might represent a promising therapy to prevent the progression of renal fibrosis.

Attenuation of Expression of Splenocytes Pro-Inflammatory Cytokines and Lung Alpha-Smooth Muscle Actin By Human Amniotic Mesenchymal Stem Cells-Conditioned Medium in Asthmatic Mice

2021 ◽  
Author(s):  
Fereshteh Dalouchi ◽  
Zeynab Sharifi Aghdam ◽  
Raza Falak ◽  
Morteza Bakhshesh ◽  
Maryam Hajidazeh ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Smooth Muscle ◽  
Inflammatory Cytokines ◽  
Smooth Muscle Actin ◽  
Inflammatory Factors ◽  
Muscle Actin ◽  
Alpha Smooth Muscle Actin ◽  
Amniotic Mesenchymal Stem Cells ◽  
Pro Inflammatory Cytokines

Abstract Background Asthma is a chronic respiratory illness characterized by lung tissue remodeling, T helper cell imbalance, and the generation of inflammatory factors. The Human amniotic mesenchymal stem cells-conditioned medium (hAM-MSC-CM) contains various immunomodulatory components and has been utilized in certain studies as a source for anti-inflammatory factors. We investigated the impacts of CM on splenocytes pro-inflammatory cytokines and alpha-smooth muscle actin (α-SMA) expression in Balb/c mice with Ovalbumin (OVA)-induced asthma.Methods and results Forty mice were separated into four groups of ten: control (challenged and sensitized with normal saline solution), asthma (sensitized on days 1, 8, and 14 and challenged daily with OVA from days 21 to 28), OVA+CM (asthmatic mice treated with CM on days 29 and 30), and OVA+DMEM (DMEM-treated asthmatic mice on days 29 and 30). The spleen and lung tissues were removed 48 hours after the final challenge, and the expression of the inflammatory factors in the splenocyte culture supernatant was determined by ELISA, while the α-SMA expression in the lung was determined using western blotting. α-SMA protein expression was significantly greater in lung tissue. Also, inflammatory agents were significantly higher in the splenocytes supernatant in the DMEM and asthma groups compared to the control group. CM therapy has been shown to inhibit the production of the α-SMA protein and inflammatory cytokines. Conclusions Results showed that CM Treatment was able to decrease the α-SMA expression in lung and splenocytes pro-inflammatory cytokines.

Bone marrow mesenchymal stem cells-derived exosomes reduce apoptosis and inflammatory response during spinal cord injury by inhibiting the TLR4/MyD88/NF-κB signaling pathway

2021 ◽  
pp. 096032712110033
Author(s):  
Liying Fan ◽  
Jun Dong ◽  
Xijing He ◽  
Chun Zhang ◽  
Ting Zhang
Keyword(s):  
Spinal Cord ◽  
Stem Cells ◽  
Bone Marrow ◽  
Spinal Cord Injury ◽  
Mesenchymal Stem Cells ◽  
Motor Function ◽  
Inflammatory Factors ◽  
Cord Injury ◽  
Marrow Mesenchymal Stem Cells ◽  
Apoptosis And Inflammation

Spinal cord injury (SCI) is one of the most common destructive injuries, which may lead to permanent neurological dysfunction. Currently, transplantation of bone marrow mesenchymal stem cells (BMSCs) in experimental models of SCI shows promise as effective therapies. BMSCs secrete various factors that can regulate the microenvironment, which is called paracrine effect. Among these paracrine substances, exosomes are considered to be the most valuable therapeutic factors. Our study found that BMSCs-derived exosomes therapy attenuated cell apoptosis and inflammation response in the injured spinal cord tissues. In in vitro studies, BMSCs-derived exosomes significantly inhibited lipopolysaccharide (LPS)-induced PC12 cell apoptosis, reduced the secretion of pro-inflammatory factors including tumor necrosis factor (TNF)-α and IL (interleukin)-1β and promoted the secretion of anti-inflammatory factors including IL-10 and IL-4. Moreover, we found that LPS-induced protein expression of toll-like receptor 4 (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear transcription factor-κB (NF-κB) was significantly downregulated after treatment with BMSCs-derived exosomes. In in vivo studies, we found that hindlimb motor function was significantly improved in SCI rats with systemic administration of BMSCs-derived exosomes. We also observed that the expression of pro-apoptotic proteins and pro-inflammatory factors was significantly decreased, while the expression of anti-apoptotic proteins and anti-inflammatory factors were upregulated in SCI rats after exosome treatment. In conclusion, BMSCs-derived exosomes can inhibit apoptosis and inflammation response induced by injury and promote motor function recovery by inhibiting the TLR4/MyD88/NF-κB signaling pathway, which suggests that BMSCs-derived exosomes are expected to become a new therapeutic strategy for SCI.

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

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.

scholarly journals Inflammatory cytokines-stimulated human muscle stem cells ameliorate ulcerative colitis via the IDO-TSG6 axis

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Shengchao Zhang ◽  
Jiankai Fang ◽  
Zhanhong Liu ◽  
Pengbo Hou ◽  
Lijuan Cao ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
Human Muscle ◽  
Enzyme Linked Immunosorbent Assay ◽  
Muscle Stem Cells ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory

Abstract Background Muscle stem cells (MuSCs) are absolutely required for the formation, repair, and regeneration of skeletal muscle tissue. Increasing evidence demonstrated that tissue stem cells, especially mesenchymal stem cells (MSCs), can exert therapeutic effects on various degenerative and inflammatory disorders based on their immunoregulatory properties. Human mesenchymal stem cells (hMSCs) treated with interferon-γ (IFN-γ) and tumor necrosis factor-α (TNF-α) were reported to possess anti-inflammatory functions by producing TNF-stimulated gene 6 (TSG-6). However, whether human muscle stem cells (hMuSCs) also possess TSG-6 mediated anti-inflammatory functions has not been explored. Methods The ulcerative colitis mouse model was established by subjecting mice to dextran sulfate sodium (DSS) in drinking water for 7 days. hMuSCs were pretreated with IFN-γ and TNF-α for 48 h and were then transplanted intravenously at day 2 of DSS administration. Body weights were monitored daily. Indoleamine 2,3-dioxygenase (IDO) and TSG-6 in hMuSCs were knocked down with short hairpin RNA (shRNA) and small interfering RNA (siRNA), respectively. Colon tissues were collected for length measurement and histopathological examination. The serum level of IL-6 in mice was measured by enzyme-linked immunosorbent assay (ELISA). Real-time PCR and Western blot analysis were performed to evaluate gene expression. Results hMuSCs treated with inflammatory factors significantly ameliorated inflammatory bowel disease (IBD) symptoms. IDO and TSG-6 were greatly upregulated and required for the beneficial effects of hMuSCs on IBD. Mechanistically, the tryptophan metabolites, kynurenine (KYN) or kynurenic acid (KYNA) produced by IDO, augmented the expression of TSG-6 through activating their common receptor aryl hydrocarbon receptor (AHR). Conclusion Inflammatory cytokines-treated hMuSCs can alleviate DSS-induced colitis through IDO-mediated TSG-6 production.

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 Tailored Hydrogels as Delivery Platforms for Conditioned Medium from Mesenchymal Stem Cells in a Model of Acute Colitis in Mice

Pharmaceutics ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1127
Author(s):  
Juan Sendon-Lago ◽  
Lorena Garcia-del Rio ◽  
Noemi Eiro ◽  
Patricia Diaz-Rodriguez ◽  
Leandro Avila ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Body Weight ◽  
Conditioned Medium ◽  
Local Treatment ◽  
Histopathological Analysis ◽  
Mrna Levels ◽  
Acute Colitis ◽  
Tnf Α ◽  
Ifn Γ

Inflammatory bowel disease (IBD), including Crohn’s disease (CD) and ulcerative colitis (UC), is increasingly prevalent and current therapies are not completely effective. Mesenchymal stem cells are emerging as a promising therapeutic option. Here, the effect of local hydrogel application loaded with conditioned medium (CM) from human uterine cervical stem cells (hUCESC-CM) in an experimental acute colitis mice model has been evaluated. Colitis induction was carried out in C57BL/6 mice by dissolving dextran sulfate sodium (DSS) in drinking water for nine days. Ulcers were treated by rectal administration of either mesalazine (as positive control) or a mucoadhesive and thermosensitive hydrogel loaded with hUCESC-CM (H-hUCESC-CM). Body weight changes, colon length, and histopathological analysis were evaluated. In addition, pro-inflammatory TNF-α, IL-6, and IFN-γ mRNA levels were measured by qPCR. Treatment with H-hUCESC-CM inhibited body weight loss and colon shortening and induced a significant decrease in colon mucosa degeneration, as well as TNF-α, IFN-γ, and IL-6 mRNA levels. Results indicate that H-hUCESC-CM effectively alleviated DSS-induced colitis in mice, suggesting that H-hUCESC-CM may represent an attractive cell-free therapy for local treatment of IBD.

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

2017 ◽  
Vol 26 (1) ◽  
pp. 4-14 ◽  
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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