scholarly journals Bone Marrow-Derived Mesenchymal Stem Cells Differentially Affect Glioblastoma Cell Proliferation, Migration, and Invasion: A 2D-DIGE Proteomic Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Shenjie Li ◽  
Wei Xiang ◽  
Junjie Tian ◽  
Haorun Wang ◽  
Shuiwang Hu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Proteomic Analysis ◽  
Differentially Expressed ◽  
Migration And Invasion ◽  
Differentially Expressed Proteins ◽  
C6 Cells ◽  
2D Dige

Bone marrow-derived mesenchymal stem cells (BM-MSCs) display high tumor tropism and cause indirect effects through the cytokines they secrete. However, the effects of BM-MSCs on the biological behaviors of glioblastoma multiforme remain unclear. In this study, the conditioned medium from BM-MSCs significantly inhibited the proliferation of C6 cells ( P < 0.05 ) but promoted their migration and invasion ( P < 0.05 ). Two-dimensional fluorescence difference gel electrophoresis (2D-DIGE) proteomic analysis revealed 17 proteins differentially expressed in C6 cells exposed to the BM-MSC-conditioned medium including five upregulated proteins and 12 downregulated proteins. Among these, six differentially expressed proteins (Calr, Set, Oat, Npm1, Ddah1, and Tardbp) were closely related to cell proliferation and differentiation, and nine proteins (Pdia6, Sphk1, Anxa4, Vim, Tuba1c, Actr1b, Actn4, Rap2c, and Tpm2) were associated with motility and the cytoskeleton, which may modulate the invasion and migration of tumor cells. Above all, by identifying the differentially expressed proteins using proteomics and bioinformatics analysis, BM-MSCs could be genetically modified to specifically express tumor-suppressive factors when BM-MSCs are to be used as tumor-selective targeting carriers in the future.

Exosomal MicroRNA-204 Derived from Bone Marrow Mesenchymal Stem Cells (BMSCs) Inhibits Cell Proliferation and Induces Apoptosis Through NF-κB Signaling Pathway in Breast Cancer

2022 ◽  
Vol 12 (2) ◽  
pp. 273-278
Author(s):  
Daqing Jiang ◽  
Xianxin Xie ◽  
Cong Wang ◽  
Weijie Li ◽  
Jianjun He
Keyword(s):  
Breast Cancer ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Cancer Cells ◽  
Breast Cancer Cells ◽  
Marrow Mesenchymal Stem Cells ◽  
Induced Apoptosis ◽  
Signaling Activation

Our study intends to assess the relationship between exosomes derived from bone marrow mesenchymal stem cells (BMSC-exo) and breast cancer. BMSC-exo were isolated and characterized by transmission electron microscopy. After transfection of BMSCs with miR-204 inhibitor, breast cancer cells were incubated with BMSC-exo followed by analysis of cell proliferation by CCK-8 assay, cell apoptosis by flow cytometry, and expression of apoptosis-related protein and NF-κB signaling by western blot. The co-culture of BMSC-exo with breast cancer cells enhanced miR-204 transcription, inhibited cell proliferation and induced apoptosis. Further, BMSC-exo accelerated apoptosis as demonstrated by the increased level of Bax and casepase-3 and decreased Bcl-2 expression, as well as reduced NF-κB signaling activity. But knockdown of miR-204 abolished the effect of BMSC-exo on apoptosis and proliferation with NF-κB signaling activation. In conclusion, miR-204 from BMSC-exo restrains growth of breast cancer cell and might be a novel target for treating breast cancer.

Purinergic Stimulation of Human Bone Marrow-Derived Mesenchymal Stem Cells Modulate Their Function and Differentiation Potential.

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3848-3848
Author(s):  
Marilena Ciciarello ◽  
Valentina Salvestrini ◽  
Davide Ferrari ◽  
Sara Gulinelli ◽  
Roberta Zini ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Transcription Factor ◽  
Human Bone ◽  
Differentiation Potential ◽  
Qrt Pcr ◽  
Differentiated Cells

Abstract Abstract 3848 Introduction: Human bone marrow derived Mesenchymal Stem Cells (hMSCs) are adult multipotent cells. hMSCs differentiate in vitro and in vivo into several tissue lineages originating from the three germinal layers making them attractive candidates for bioengineering and cellular therapy. Thus, it seems of great relevance to search putative messengers and signalling able to modulate their proliferation and differentiation. Nucleotides triphosphates are extracellular messengers binding to specific receptors (P2Rs) that modulate cell functions depending on the cell type. Controversial information is available on P2 expression and activity in hMSCs. Methods and Results: Here we found that hMSCs expressed several P2R subtypes. hMSCs were very resistant to the cytotoxic effects of high concentrations of ATP, as demonstrated by the lack of morphological and mitochondrial changes or release of intracellular markers of cell death. Gene expression profiling revealed that ATP treatment down-regulated cell proliferation and up-regulated cell migration genes in hMSCs. Functional studies confirmed the inhibitory activity of ATP on proliferation and clonogenic ability of hMSCs. Furthermore, ATP potentiated the chemotactic response of hMSCs to the chemokine CXCL12, and increased their spontaneous migration. In vivo, xenotransplant experiments showed that the homing capacity of hMSCs to murine bone marrow was increased by ATP pre-treatment. Moreover, ATP increased pro-inflammatory cytokines production (IL-2, IFN-g, IL-12p70), while decreased secretion of the anti-inflammatory cytokine IL-10. This finding was associated with the reduced ability of ATP-treated hMSC of inhibiting T-cell proliferation. Microarrays data suggested that several genes implicated in hMSC differentiation can be modulated by ATP treatment. To further investigate this issue, hMSCs cells were cultured under adipogenic or osteogenic conditions and were transiently exposed to ATP before starting differentiation or continuously exposed to ATP for the first 3 days of differentiation induction. We demonstrated that adipogenesis-related accumulation of lipids, analyzed by Oil red O staining, was more evident in ATP treated cultures. Furthermore, quantitative real time PCR (qRT-PCR) assay showed that mRNA expression of PPARg, a transcription factor early up-regulated during adipogenesis, was significantly increased in hMSCs differentiated cells treated with ATP. In osteogenic condition, analysis of mineralized area through Alizarin Red staining, indicated that ATP treatment enhanced the extent of mineralization compared to untreated control. The expression of RUNX2, a key transcription factor in osteogenesis, analyzed by qRT-PCR in differentiated cells confirmed data obtained in Alizarin-based assay. Conclusions: These data demonstrated that purinergic signalling modulates biological functions and differentiation potential of hMSCs. Disclosures: No relevant conflicts of interest to declare.

Effect of αCGRP on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells Through Smad/Runx2 Signaling Pathway

2020 ◽  
Vol 10 (6) ◽  
pp. 868-873
Author(s):  
Shengxiang Huang ◽  
Haibo Mei ◽  
Rongguo He ◽  
Kun Liu ◽  
Jin Tang ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Osteogenic Differentiation ◽  
Real Time ◽  
Real Time Pcr ◽  
Caspase 3 ◽  
Alp Activity ◽  
Marrow Mesenchymal Stem Cells

The α-calcitonin gene-related peptide (α-CGRP) regulates bone metabolism and has potential applications in enhancing bone remodeling in vivo. However, α-CGRP's role in bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation remain unclear. Rat BMSCs were separated into control group, α-CGRP group and α-CGRP siRNA group, in which BMSCs were transfected with α-CGRP plasmid and α-CGRP siRNA respectively followed by analysis of α-CGRP level by real time PCR and ELISA, cell proliferation by MTT assay, Caspase 3 activity, ALP activity, formation of calcified nodules by alizarin red staining, Smad1 and Smad7 level by Western blot and Runx2 by real time PCR. αCGRP transfection into BMSCs significantly up-regulated CGRP, which could promote cell proliferation, inhibit Caspase 3 activity, promote ALP activity, increase calcified nodules formation and upregulate Smad1, Smad7 and Runx2 compared to control (P < 0.05); transfection of αCGRP siRNA significantly down-regulated CGRP in BMSCs, inhibited cell proliferation, promoted Caspase 3 activity, inhibited ALP activity, inhibited calcified nodules formation and downregulate Smad1, Smad7 and Runx2 (P < 0.05). αCGRP overexpression promotes the Smad/Runx2 signaling, which in turn promotes BMSCs proliferation and osteogenesis. Decreased αCGRP level inhibits Smad/Runx2 signaling, promotes BMSCs apoptosis, inhibits proliferation and osteogenic differentiation.

Effect of SOX9 on Osteogenic Differentiation of Bone Marrow Mesenchymal Stem Cells Through WNTβ/Catenin Pathway

2019 ◽  
Vol 9 (10) ◽  
pp. 1429-1434
Author(s):  
Qing Yang ◽  
Cheng Li ◽  
Manli Yan ◽  
Chunhua Fang
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Protein Expression ◽  
Osteogenic Differentiation ◽  
Real Time ◽  
Real Time Pcr ◽  
Alp Activity ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) can be differentiated into different types of cells. SOX9 involves in the development and progression of various diseases. Our study aims to assess SOX9's effect on osteogenic differentiation of BMSCs and its related regulatory mechanisms. Rat BMSCs were isolated and randomly divided into control group, SOX9 group and SOX9 siRNA group, which was transfected with pcDNA-SOX9 plasmid or SOX9 siRNA respectively followed by analysis of SOX9 expression by Real time PCR, cell proliferation by MTT assay, Caspase3 and ALP activity, GSK-3β expression and Wntβ/Catenin Signaling pathway protein expression by Western blot, and expression of osteogenic genes Runx2 and BMP-2 by Real time PCR. Transfection of pcDNA-SOX9 plasmid into BMSCs significantly inhibited cell proliferation, promoted Caspase3 activity, decreased ALP activity and downregulated Runx2 and BMP-2, increased GSK-3β expression and decreased Wntβ/Catenin expression protein expression (P< 0.05). SOX9 siRNA transfection significantly promoted cell proliferation, inhibited Caspase3 activity, increased ALP activity and upregulated Runx2 and BMP-2, downregulated GSK-3β and increased Wntβ/Catenin expression. SOX9 regulates BMSCs proliferation and osteogenic differentiation through Wntβ/Catenin signaling pathway.

Effect of Substance P on Bone Marrow Mesenchymal Stem Cells Differentiation in High Glucose Environment

2020 ◽  
Vol 10 (2) ◽  
pp. 252-258
Author(s):  
HeTong Yu ◽  
Yanjun Li ◽  
Xiaowei Ren ◽  
Huanhuan Zhao ◽  
Chong Nan ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Substance P ◽  
High Glucose ◽  
Mtor Signaling ◽  
Alp Activity ◽  
Ampk Phosphorylation ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) can be used to treat bone defects. The neuropeptide substance P (SP) plays an important role in a variety of life activities. However, the effect of SP on BMSCs differentiation in high glucose environment remains unclear. Rat BMSCs were isolated and divided into control group; high glucose group; and SP group. The secretion of SP was detected by ELISA; cell proliferation was detected by MTT assay; apoptosis activity was detected by Cas-pase3 activity kit. Real time PCR was performed to measure Bax and Bcl-2 expression. Alizarin red staining was to detect calcified nodule formation. Western blot was done to measure AMPK/mTOR signaling protein expression. In high glucose environment, SP secretion was significantly decreased, along with increased cell proliferation, Caspase3 activity and Bax expression. Meanwhile, Bcl-2 expression, ALP activity and calcified nodules formation was significantly decreased with reduced AMPK phosphorylation and increased mTOR expression (P < 0.05). SP addition in high glucose environment significantly promoted SP secretion and cell proliferation, decreased Caspase3 activity and Bax expression, increased Bcl-2 expression, ALP activity and calcification nodules formation with increased AMPK phosphorylation and decreased mTOR expression (P < 0.05). In high glucose environment, SP secretion is decreased in BMSCs. Up-regulation of SP in BMSCs cells in high glucose environment inhibit the apoptosis of BMSCs and promote cell proliferation and osteogenesis by regulating AMPK/mTOR signaling pathway.

Human bone marrow mesenchymal stem cells suppress the proliferation of hepatic stellate cells by inhibiting the ubiquitination of p27

2017 ◽  
Vol 95 (6) ◽  
pp. 628-633 ◽  
Author(s):  
Liang Wang ◽  
Guang Bai ◽  
Fei Chen
Keyword(s):  
Cell Cycle ◽  
Stem Cells ◽  
Bone Marrow ◽  
Cell Proliferation ◽  
Mesenchymal Stem Cells ◽  
Cell Cycle Arrest ◽  
Hepatic Stellate Cells ◽  
Stellate Cells ◽  
Cycle Arrest ◽  
Marrow Mesenchymal Stem Cells

Bone marrow mesenchymal stem cells (BMSCs) have considerable therapeutic potential for the treatment of end-stage liver disease. Previous studies have demonstrated that BMSCs secrete growth factors and cytokines that inactivate hepatic stellate cells (HSCs), which inhibited the progression of hepatic fibrosis. The aim of this study was to determine the mechanism by which BMSCs suppress the function of HSCs in fibrosis. Our results showed that co-culture of BMSCs and HSCs induced cell cycle arrest at the G10/G1 phase and cell apoptosis of HSCs, which finally inhibited the cell proliferation of HSCs. Consistent with the cell cycle arrest, co-culture of BMSCs and HSCs increased the abundance of the cell cycle protein p27. Mechanistically, we further uncovered that following the co-culture with BMSCs, the expression level of the E3 ligase S-phase kinase-associated protein 2 (SKP2) that is responsible for the ubiquitination of p27 was decreased, which attenuated the ubiquitination of p27 and increased the stability of p27 in HSCs. Collectively, our results indicated the potential involvement of the SKP2–p27 axis for the inhibitory effect of BSMCs on the cell proliferation of HSCs.

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