scholarly journals Inflammatory Regulation by TNF-α-Activated Adipose-Derived Stem Cells in the Human Bladder Cancer Microenvironment

2021 ◽  
Vol 22 (8) ◽  
pp. 3987
Author(s):  
Hui-Kung Ting ◽  
Chin-Li Chen ◽  
En Meng ◽  
Juin-Hong Cherng ◽  
Shu-Jen Chang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bladder Cancer ◽  
Adipose Derived Stem Cells ◽  
Tnf Α ◽  
Paracrine Growth Factors ◽  
Inflammatory Regulation ◽  
Cell Medium ◽  
Insight Into ◽  
Necrosis Factor ◽  
Apoptosis Ratio

Mesenchymal stem cells (MSCs), such as adipose-derived stem cells (ADSCs), have the most impressive ability to reduce inflammation through paracrine growth factors and cytokines that participate in inflammation. Tumor necrosis factor (TNF)-α bioactivity is a prerequisite in several inflammatory and autoimmune disease models. This study investigated the effects of TNF-α stimulate on ADSCs in the tumor microenvironment. The RNAseq analysis and cytokines assay demonstrated that TNF-α stimulated ADSCs proliferation and pro-inflammatory genes that correlated to leukocytes differentiation were upregulated. We found that upregulation of TLR2 or PTGS2 toward to IRF7 gene-associated with immunomodulatory and antitumor pathway under TNF-α treatment. In TNF-α–treated ADSCs cultured with the bladder cancer (BC) cell medium, the results showed that apoptosis ratio and OCT-4 and TLR2 genes which maintained the self-renewal ability of stem cells were decreased. Furthermore, the cell survival regulation genes including TRAF1, NF-kB, and IRF7 were upregulated in TNF-α–treated ADSCs. Additionally, these genes have not been upregulated in BC cell medium. A parallel study showed that tumor progressing genes were downregulated in TNF-α–treated ADSCs. Hence, the study suggests that TNF-α enhances the immunomodulatory potential of ADSCs during tumorigenesis and provides insight into highly efficacious MSC-based therapeutic options for BC.

scholarly journals The interplay between adipose-derived stem cells and bladder cancer cells

2018 ◽  
Vol 8 (1) ◽  
Author(s):  
Malgorzata Maj ◽  
Anna Kokocha ◽  
Anna Bajek ◽  
Tomasz Drewa
Keyword(s):  
Stem Cells ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Adipose Derived Stem Cells ◽  
Bladder Cancer Cells

scholarly journals Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

2020 ◽  
Vol 9 (6) ◽  
pp. 1711 ◽  
Author(s):  
Adrien A. Eshraghi ◽  
Emre Ocak ◽  
Angela Zhu ◽  
Jeenu Mittal ◽  
Camron Davies ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Inner Ear ◽  
Cell Damage ◽  
Tunel Staining ◽  
Tnf Α ◽  
Rat Cochlea ◽  
Necrosis Factor

Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

scholarly journals Nanoparticle engineered TRAIL-overexpressing adipose-derived stem cells target and eradicate glioblastoma via intracranial delivery

2016 ◽  
Vol 113 (48) ◽  
pp. 13857-13862 ◽  
Author(s):  
Xinyi Jiang ◽  
Sergio Fitch ◽  
Christine Wang ◽  
Christy Wilson ◽  
Jianfeng Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Xenograft Model ◽  
Adipose Derived Stem Cells ◽  
Drug Delivery Vehicles ◽  
Effective Strategies ◽  
Polymeric Nanoparticle ◽  
Promising Therapeutic Approach ◽  
Delivery Vehicles ◽  
Necrosis Factor

Glioblastoma multiforme (GBM) is one of the most intractable of human cancers, principally because of the highly infiltrative nature of these neoplasms. Tracking and eradicating infiltrating GBM cells and tumor microsatellites is of utmost importance for the treatment of this devastating disease, yet effective strategies remain elusive. Here we report polymeric nanoparticle-engineered human adipose-derived stem cells (hADSCs) overexpressing tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) as drug-delivery vehicles for targeting and eradicating GBM cells in vivo. Our results showed that polymeric nanoparticle-mediated transfection led to robust up-regulation of TRAIL in hADSCs, and that TRAIL-expressing hADSCs induced tumor-specific apoptosis. When transplanted in a mouse intracranial xenograft model of patient-derived glioblastoma cells, hADSCs exhibited long-range directional migration and infiltration toward GBM tumor. Importantly, TRAIL-overexpressing hADSCs inhibited GBM growth, extended survival, and reduced the occurrence of microsatellites. Repetitive injection of TRAIL-overexpressing hADSCs significantly prolonged animal survival compared with single injection of these cells. Taken together, our data suggest that nanoparticle-engineered TRAIL-expressing hADSCs exhibit the therapeutically relevant behavior of “seek-and-destroy” tumortropic migration and could be a promising therapeutic approach to improve the treatment outcomes of patients with malignant brain tumors.

scholarly journals 1,25(OH)2D3 Differently Affects Immunomodulatory Activities of Mesenchymal Stem Cells Depending on the Presence of TNF-α, IL-1β and IFN-γ

2019 ◽  
Vol 8 (12) ◽  
pp. 2211 ◽  
Author(s):  
Christian Behm ◽  
Alice Blufstein ◽  
Johannes Gahn ◽  
Barbara Kubin ◽  
Michael Nemec ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cytokines ◽  
T Lymphocyte ◽  
T Lymphocyte Proliferation ◽  
Tnf Α ◽  
Ifn Γ ◽  
Anti Inflammatory ◽  
Anti Inflammatory Cytokine ◽  
Necrosis Factor

Periodontal ligament-derived mesenchymal stem cells (hPDLSCs) possess immunomodulatory abilities which are strongly enhanced by various inflammatory cytokines. Vitamin D3 has anti-inflammatory effects on hPDLSCs and immune cells. However, no study to date has directly compared the influence of 1,25(OH)2D3 on the immunomodulatory activities of hPDLSCs in the presence of different cytokines. In the present study, the effects of hPDLSCs treated with tumor necrosis factor (TNF)-α, interleukin (IL)-1β, or interferon (IFN)-γ in the presence of 1,25(OH)2D3 on the proliferation of allogenic CD4+ T lymphocyte or on the functional status of primary CD68+ macrophages were analyzed in coculture models. Additionally, the effects of 1,25(OH)2D3 on TNF-α-, IL-1β-, and IFN-γ-induced gene expression of some immunomodulatory factors in hPDLSCs were compared. Under coculture conditions, 1,25(OH)2D3 increased or decreased CD4+ T lymphocyte proliferation via hPDLSCs, depending on the cytokine. hPDLSCs primed with 1,25(OH)2D3 and different cytokines affected pro- and anti-inflammatory cytokine expression in macrophages variably, depending on the priming cytokine. With one exception, 1,25(OH)2D3 significantly reduced TNF-α-, IL-1β-, and IFN-γ-induced expression of all the investigated immunomediators in hPDLSCs, albeit to different extents. These results suggest that 1,25(OH)2D3 influences the immunomodulatory activities of hPDLSCs depending qualitatively and quantitatively on the presence of certain inflammatory cytokines.

scholarly journals Tnfaip6 Secreted by Bone Marrow–Derived Mesenchymal Stem Cells Attenuates TNBS-Induced Colitis by Modulating Follicular Helper T Cells and Follicular Regulatory T Cells Balance in Mice

2021 ◽  
Vol 12 ◽  
Author(s):  
Guangli Gu ◽  
Xiaodan Lv ◽  
Gengfeng Liu ◽  
Ruizhi Zeng ◽  
Shiquan Li ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Weight Loss ◽  
T Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Necrosis ◽  
Helper T Cells ◽  
Follicular Helper ◽  
Tnf Α ◽  
Necrosis Factor

Objective: To investigate the immunological mechanism of bone marrow–derived mesenchymal stem cells (BM-MSCs) in inflammatory bowel disease (IBD).Methods: Mice with 2,4,6-trinitrobenzene sulfonic acid (TNBS)–induced colitis were intraperitoneally injected with phosphate-buffered saline, BM-MSCs, BM-MSCs with tumor necrosis factor–induced protein 6 (Tnfaip6) knockdown mediated by RNA interference recombinant adenovirus, and BM-MSCs–infected with control adenovirus or recombinant mouse Tnfaip6. The disease activity index, weight loss, and histological scores were recorded. Serum levels of Tnfaip6 and pro- and anti-inflammatory cytokines, including interleukin (IL)-21, tumor necrosis factor-alpha (TNF-α), IL-10 were measured by enzyme-linked immunosorbent assay. The relative expression levels of these cytokines, B-cell lymphoma 6 (BCL-6) and fork-like transcription factor p3 (Foxp3) in the colon were determined by real-time quantitative PCR (RT-qPCR). BCL-6 and Foxp3 are the master regulators of follicular helper T cells (Tfh) and follicular regulatory T cells (Tfr), respectively. The infiltration of Tfh and Tfr in mesenteric lymph nodes (MLNs) and spleens was analyzed by flow cytometry.Results: Compared to the normal control group, the expression levels of BCL-6 and IL-21 in the colon, Tfh infiltration, and ratios of Tfh/Tfr in the MLNs and spleen, and the serum concentrations of IL-21 and TNF-α increased significantly in the colitis model group (p < 0.05). Intraperitoneal injection of BM-MSCs or Tnfaip6 ameliorated weight loss and clinical and histological severity of colitis, downregulated the expression of BCL-6, IL-21, and TNF-α, upregulated the expression of Foxp3, IL-10, and Tnfaip6 (p < 0.05), increased Tfr and reduced the infiltration of Tfh in the MLNs and spleen, and downregulated the Tfh/Tfr ratio (p < 0.05). On the other hand, BM-MSCs lost the therapeutic effect and immune regulatory functions on Tfh and Tfr after Tnfaip6 knockdown.Conclusion: Tfh increase in the inflamed colon, Tfh decrease and Tfr increase during the colitis remission phase, and the imbalance of the Tfh/Tfr ratio is closely related to the progression of IBD. Tnfaip6 secreted by BM-MSCs alleviates IBD by inhibiting Tfh differentiation, promoting Tfr differentiation, and improving the imbalance of Tfh/Tfr in mice.

scholarly journals miR-539 activates the SAPK/JNK signaling pathway to promote ferropotosis in colorectal cancer by directly targeting TIPE

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Yan Yang ◽  
Zeyang Lin ◽  
Zhaopu Han ◽  
Zhengxin Wu ◽  
Jianyu Hua ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
High Recurrence Rate ◽  
The Novel ◽  
Potential Therapeutic Target ◽  
Tnf Α ◽  
Jnk Signaling Pathway ◽  
The Relationship ◽  
Insight Into ◽  
Necrosis Factor

AbstractColorectal cancer (CRC) is a common tumor that harms human health with a high recurrence rate. It has been reported that the expression of microRNA-539 (miR-539) is low in several types of cancer, including CRC. Tumor necrosis factor (TNF)-α-induced protein 8 (TNFAIP8/TIPE) is highly expressed in CRC and promotes the proliferation, migration and angiogenesis of CRC. However, the relationship between miR-539 and TIPE and the mechanisms by which they regulate the proliferation of CRC remain to be explored. We aimed to investigate the functions and mechanisms of miR-539 in CRC proliferation. Functionally, miR-539 can bind to and regulate the expression of TIPE, and miR-539 activates SAPK/JNK to downregulate the expression of glutathione peroxidase 4 (GPX4) and promote ferroptosis. Our data reveal the novel role of miR-539 in regulating ferroptosis in CRC via activation of the SAPK/JNK axis, providing new insight into the mechanism of abnormal proliferation in CRC and a novel potential therapeutic target for advanced CRC.

The let-7f-5p–Nme4 pathway mediates tumor necrosis factor α-induced impairment in osteogenesis of bone marrow-derived mesenchymal stem cells

2021 ◽  
pp. 1-11
Author(s):  
Ying-Jie Zhao ◽  
Zheng-Chao Gao ◽  
Xi-Jing He ◽  
Jing Li
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Tumor Necrosis Factor ◽  
Osteogenic Differentiation ◽  
Tumor Necrosis ◽  
Tumor Necrosis Factor Α ◽  
Tnf Α ◽  
Factor Α ◽  
Necrosis Factor

Although tumor necrosis factor α (TNF-α)-mediated inflammation significantly impacts osteoporosis, the mechanisms underlying the osteogenic differentiation defects of bone marrow-derived mesenchymal stem cells (BM-MSCs) caused by TNF-α remain poorly understood. We found that TNF-α stimulation of murine BM-MSCs significantly upregulated the expression levels of several microRNAs (miRNAs), including let-7f-5p, but this increase was significantly reversed by treatment with the kinase inhibitor BAY 11-7082. To study gain- or loss of function, we transfected cells with an miRNA inhibitor or miRNA mimic. We then demonstrated that let-7f-5p impaired osteogenic differentiation of BM-MSCs in the absence and presence of TNF-α, as evidenced by alkaline phosphatase and alizarin red staining as well as quantitative assays of the mRNA levels of bone formation marker genes in differentiated BM-MSCs. Moreover, let-7f-5p targets the 3′ untranslated region of Nucleoside diphosphate kinase 4 (Nme4) mRNA and negatively regulates Nme4 expression in mouse BM-MSCs. Ectopic expression of Nme4 completely reversed the inhibitory effects of the let-7f-5p mimic on osteogenic differentiation of mouse BM-MSCs. Furthermore, inhibition of let-7f-5p or overexpression of Nme4 in BM-MSCs restored in-vivo bone formation in an ovariectomized animal model. Collectively, our work indicates that let-7f-5p is involved in TNF-α-mediated reduction of BM-MSC osteogenesis via targeting Nme4.

The effects of adipose‐derived stem cells on CD133‐expressing bladder cancer cells

2019 ◽  
Vol 120 (7) ◽  
pp. 11562-11572 ◽  
Author(s):  
Malgorzata Maj ◽  
Anna Kokocha ◽  
Anna Bajek ◽  
Tomasz Drewa
Keyword(s):  
Stem Cells ◽  
Bladder Cancer ◽  
Cancer Cells ◽  
Adipose Derived Stem Cells ◽  
Bladder Cancer Cells

scholarly journals lncRNA-KCNQ1OT1: A Potential Target in Exosomes Derived from Adipose-Derived Stem Cells for the Treatment of Osteoporosis

2021 ◽  
Vol 2021 ◽  
pp. 1-17
Author(s):  
Shan-zheng Wang ◽  
Jun Jia ◽  
Chang-hong Chen
Keyword(s):  
Stem Cells ◽  
Noncoding Rna ◽  
Caspase 3 ◽  
Luciferase Reporter Assay ◽  
Cell Counting ◽  
Luciferase Reporter ◽  
Adipose Derived Stem Cells ◽  
Reporter Assay ◽  
Tnf Α ◽  
Primary Osteoblasts

Background. Osteoporosis is a worldwide medical and socioeconomic burden characterized by systemic impairment of bone strength and microstructure. Exosomes derived from adipose-derived stem cells (ADSCs-Exos) have been confirmed to play effective roles in the repair of various tissues and organs. This study was aimed at investigating the role of ADSCs-Exos and a novel long noncoding RNA KCNQ1OT1 played in osteoporosis as well as the underlying mechanism. Methods. Primary osteoblasts were treated with different doses of tumor necrosis factor-α (TNF-α) (0, 1, 2.5, 5, and 10 ng/ml) and then cocultured with ADSCs-Exos or exosome-derived from lnc-KCNQ1OT1-modified ADSCs (KCNQ1OT1-Exos). The expression of miRNA-141-5p (miR-141-5p) and lnc-KCNQ1OT1 was evaluated by quantitative real-time polymerase chain reaction (qRT-PCR). The protein expression of cleaved-caspase-3, caspase-3, and Bax was determined by Western blot. Cell viability and apoptosis were assessed by Cell Counting Kit-8 (CCK-8) and flow cytometry analysis, respectively. The binding sites between KCNQ1OT1 and miR-141-5p were validated by dual-luciferase reporter assay. Results. TNF-α dose-dependently increased miR-141-5p expression, inhibited viability, and promoted apoptosis of osteoblasts. However, miR-141-5p silencing or cocultured with ADSCs-Exos attenuated these effects. In addition, KCNQ1OT1-Exos could more significantly attenuate the induced cytotoxicity and apoptosis compared to ADSCs-Exos. Moreover, miR-141-5p was confirmed as the target of KCNQ1OT1 by luciferase reporter assay. Conclusions. ADSCs-Exos can attenuate cytotoxicity and apoptosis of TNF-α-induced primary osteoblasts. KCNQ1OT1-Exos have a more significant inhibitory effect compared to ADSCs-Exos by the function of sponging miR-141-5p, suggesting that KCNQ1OT1-Exos can be promising agents in osteoporosis treatment.

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