scholarly journals The Dynamic Roles of Mesenchymal Stem Cells in Colon Cancer

2018 ◽  
Vol 2018 ◽  
pp. 1-8 ◽  
Author(s):  
Shan Wang ◽  
Zhiguo Miao ◽  
Qiyuan Yang ◽  
Yimin Wang ◽  
Jinzhou Zhang
Keyword(s):  
Stem Cells ◽  
Colon Cancer ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Tumor Therapy ◽  
Potential Functions ◽  
Cell Group ◽  
Potential Candidate ◽  
Structural Support ◽  
Metastatic Sites

Colon cancer is still one of the most common causes of cancer in human and is characterized by lymphocyte infiltrates and originates from the epithelial cells found in the lining of colon or rectum of the gastrointestinal tract. Mesenchymal stem cells (MSCs) are composed of the multipotent stem cell group of stroma and can be differentiated as various cell lineages, such as fibroblasts, osteoblasts, and adipocytes. MSCs provide mechanical and structural support and have potential functions during tumor growth and metastasis. The efficacy of MSC-based therapies is partly dependent on the migration and homing of MSCs to tumors and metastatic sites. However, their migratory and engraftment potential is poorly understood. In this review, the characteristics and mechanisms of MSC’s dynamic interaction with colon cancer were summarized, particularly the potential functions of MSCs on colon cancer, including its role in improving tumor growth and as a potential candidate for tumor therapy. Understanding MSC homing provides new insights into the manipulation of MSC and the improvement of their efficacy for colon cancer therapy.

scholarly journals Let-7f miRNA regulates SDF-1α- and hypoxia-promoted migration of mesenchymal stem cells and attenuates mammary tumor growth upon exosomal release

2021 ◽  
Vol 12 (6) ◽  
Author(s):  
Virginia Egea ◽  
Kai Kessenbrock ◽  
Devon Lawson ◽  
Alexander Bartelt ◽  
Christian Weber ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Molecular Mechanisms ◽  
Hypoxia Inducible Factor ◽  
Human Mesenchymal Stem Cells ◽  
Target Cells ◽  
Autophagic Flux ◽  
Stromal Cell Derived Factor

AbstractBone marrow-derived human mesenchymal stem cells (hMSCs) are recruited to damaged or inflamed tissues where they contribute to tissue repair. This multi-step process involves chemokine-directed invasion of hMSCs and on-site release of factors that influence target cells or tumor tissues. However, the underlying molecular mechanisms are largely unclear. Previously, we described that microRNA let-7f controls hMSC differentiation. Here, we investigated the role of let-7f in chemotactic invasion and paracrine anti-tumor effects. Incubation with stromal cell-derived factor-1α (SDF-1α) or inflammatory cytokines upregulated let-7f expression in hMSCs. Transfection of hMSCs with let-7f mimics enhanced CXCR4-dependent invasion by augmentation of pericellular proteolysis and release of matrix metalloproteinase-9. Hypoxia-induced stabilization of the hypoxia-inducible factor 1 alpha in hMSCs promoted cell invasion via let-7f and activation of autophagy. Dependent on its endogenous level, let-7f facilitated hMSC motility and invasion through regulation of the autophagic flux in these cells. In addition, secreted let-7f encapsulated in exosomes was increased upon upregulation of endogenous let-7f by treatment of the cells with SDF-1α, hypoxia, or induction of autophagy. In recipient 4T1 tumor cells, hMSC-derived exosomal let-7f attenuated proliferation and invasion. Moreover, implantation of 3D spheroids composed of hMSCs and 4T1 cells into a breast cancer mouse model demonstrated that hMSCs overexpressing let-7f inhibited tumor growth in vivo. Our findings provide evidence that let-7f is pivotal in the regulation of hMSC invasion in response to inflammation and hypoxia, suggesting that exosomal let-7f exhibits paracrine anti-tumor effects.

scholarly journals Close Interactions between Mesenchymal Stem Cells and Neuroblastoma Cell Lines Lead to Tumor Growth Inhibition

PLoS ONE ◽  
2012 ◽  
Vol 7 (10) ◽  
pp. e48654 ◽  
Author(s):  
Giovanna Bianchi ◽  
Fabio Morandi ◽  
Michele Cilli ◽  
Antonio Daga ◽  
Chiara Bocelli-Tyndall ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Growth Inhibition ◽  
Cell Lines ◽  
Neuroblastoma Cell ◽  
Tumor Growth Inhibition ◽  
Neuroblastoma Cell Lines

scholarly journals Tumor-Targeted Immunotherapy by Using Primary Adipose-Derived Stem Cells and an Antigen-Specific Protein Vaccine

Cancers ◽  
2018 ◽  
Vol 10 (11) ◽  
pp. 446 ◽  
Author(s):  
Jui-Hua Lu ◽  
Bou-Yue Peng ◽  
Chun-Chao Chang ◽  
Navneet Dubey ◽  
Wen-Cheng Lo ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Antitumor Activity ◽  
Clinical Application ◽  
Public Health Problem ◽  
Specific Protein ◽  
Major Public Health Problem ◽  
Potential Candidate ◽  
Adipose Derived Stem Cells ◽  
Protein Vaccine

Cancer is a leading cause of mortality and a major public health problem worldwide. For biological therapy against cancer, we previously developed a unique immunotherapeutic platform by combining mesenchymal stem cells with an antigen-specific protein vaccine. However, this system possesses a few limitations, such as improperly immortalized mesenchymal stem cells (MSCs) along with transfected oncogenic antigens in them. To overcome the limitations of this platform for future clinical application, we freshly prepared primary adipose-derived stem cells (ADSCs) and modified the E7’ antigen (E7’) as a non-oncogenic protein. Either subcutaneously co-inoculated with cancer cells or systemically administered after tumor growth, ADSC labeled with enhanced green fluorescent protein (eGFP) and combined with modified E7’ (ADSC-E7’-eGFP) cells showed significant antitumor activity when combined with the protein vaccine in both colon and lung cancer in mice. Specifically, this combined therapy inhibited tumor through inducing cell apoptosis. The significantly reduced endothelial cell markers, CD31 and vascular endothelial growth factor (VEGF), indicated strongly inhibited tumor angiogenesis. The activated immune system was demonstrated through the response of CD4+ T and natural killer (NK) cells, and a notable antitumor activity might be contributed by CD8+ T cells. Conclusively, these evidences imply that this promising immunotherapeutic platform might be a potential candidate for the future clinical application against cancer.

scholarly journals The Potential Role of Human NME1 in Neuronal Differentiation of Porcine Mesenchymal Stem Cells: Application of NB-hNME1 as a Human NME1 Suppressor

2021 ◽  
Vol 22 (22) ◽  
pp. 12194
Author(s):  
Jin Hyoung Cho ◽  
Won Seok Ju ◽  
Sang Young Seo ◽  
Bo Hyun Kim ◽  
Ji-Su Kim ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Neuronal Differentiation ◽  
Nucleoside Diphosphate Kinase ◽  
Inhibitory Effect ◽  
Human Macrophage ◽  
Potential Candidate ◽  
Xenograft Rejection ◽  
Ganglioside Gd3

This study aimed to investigate the effects of the human macrophage (MP) secretome in cellular xenograft rejection. The role of human nucleoside diphosphate kinase A (hNME1), from the secretome of MPs involved in the neuronal differentiation of miniature pig adipose tissue-derived mesenchymal stem cells (mp AD-MSCs), was evaluated by proteomic analysis. Herein, we first demonstrate that hNME1 strongly binds to porcine ST8 alpha-N-acetyl-neuraminide alpha-2,8-sialyltransferase 1 (pST8SIA1), which is a ganglioside GD3 synthase. When hNME1 binds with pST8SIA1, it induces degradation of pST8SIA1 in mp AD-MSCs, thereby inhibiting the expression of ganglioside GD3 followed by decreased neuronal differentiation of mp AD-MSCs. Therefore, we produced nanobodies (NBs) named NB-hNME1 that bind to hNME1 specifically, and the inhibitory effect of NB-hNME1 was evaluated for blocking the binding between hNME1 and pST8SIA1. Consequently, NB-hNME1 effectively blocked the binding of hNME1 to pST8SIA1, thereby recovering the expression of ganglioside GD3 and neuronal differentiation of mp AD-MSCs. Our findings suggest that mp AD-MSCs could be a potential candidate for use as an additive, such as an immunosuppressant, in stem cell transplantation.

scholarly journals Osteogenic Differentiation of Human Mesenchymal Stem Cells Modulated by Surface Manganese Chemistry in SLA Titanium Implants

2022 ◽  
Vol 2022 ◽  
pp. 1-13
Author(s):  
Jin-Woo Park ◽  
Yusuke Tsutsumi ◽  
Eui-Kyun Park
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
Corrosion Resistance ◽  
Osteogenic Differentiation ◽  
Chemical Treatment ◽  
Human Mesenchymal Stem Cells ◽  
Titanium Implants ◽  
Potential Candidate ◽  
Implant Surface ◽  
Wet Chemical

The manganese (Mn) ion has recently been probed as a potential candidate element for the surface chemistry modification of titanium (Ti) implants in order to develop a more osteogenic surface with the expectation of taking advantage of its strong binding affinity to the integrins on bone-forming cells. However, the exact mechanism of how Mn enhances osteogenesis when introduced into the surface of Ti implants is not clearly understood. This study investigated the corrosion resistance and potential osteogenic capacity of a Mn-incorporated Ti surface as determined by electrochemical measurement and examining the behaviors of human mesenchymal stem cells (MSCs) in a clinically available sandblasted/acid-etched (SLA) oral implant surface intended for future biomedical applications. The surface that resulted from wet chemical treatment exhibited the formation of a Mn-containing nanostructured TiO2 anatase thin film in the SLA implant and improved corrosion resistance. The Mn-incorporated SLA surface displayed sustained Mn ion release and enhanced osteogenesis-related MSC function, which enhanced early cellular events such as spreading, focal adhesion, and mRNA expression of critical adhesion-related genes and promoted full human MSC differentiation into mature osteoblasts. Our findings indicate that surface Mn modification by wet chemical treatment is an effective approach to produce a Ti implant surface with increased osteogenic capacity through the promotion of the osteogenic differentiation of MSCs. The improved corrosion resistance of the resultant surface is yet another important benefit of being able to provide favorable osseointegration interface stability with an increased barrier effect.

Exosomes derived from human bone marrow mesenchymal stem cells promote tumor growth in vivo

2012 ◽  
Vol 315 (1) ◽  
pp. 28-37 ◽  
Author(s):  
Wei Zhu ◽  
Ling Huang ◽  
Yahong Li ◽  
Xu Zhang ◽  
Jianmei Gu ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Tumor Growth ◽  
Human Bone ◽  
Human Bone Marrow ◽  
Promote Tumor Growth ◽  
Marrow Mesenchymal Stem Cells

scholarly journals The Effects of Mesenchymal Stem Cells on Antimelanoma Immunity Depend on the Timing of Their Administration

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Dragana Miloradovic ◽  
Dragica Miloradovic ◽  
Bojana Simovic Markovic ◽  
Aleksandar Acovic ◽  
Carl Randall Harrell ◽  
...  
Keyword(s):  
Stem Cells ◽  
Mesenchymal Stem Cells ◽  
T Lymphocytes ◽  
Tumor Growth ◽  
Nk Cells ◽  
Plasma Levels ◽  
Th17 Cells ◽  
Antitumor Immunity ◽  
Granzyme B ◽  
Lower Plasma

There is still a lively debate about whether mesenchymal stem cells (MSCs) promote or suppress antitumor immune response. Although several possible explanations have been proposed, including different numbers of injected and engrafted MSCs, heterogeneity in phenotype, and function of tumor cells, the exact molecular mechanisms responsible for opposite effects of MSCs in modulation of antitumor immunity are still unknown. Herewith, we used a B16F10 murine melanoma model to investigate whether timing of MSC administration in tumor-bearing mice was crucially important for their effects on antitumor immunity. MSCs, intravenously injected 24 h after melanoma induction (B16F10+MSC1d-treated mice), significantly enhanced natural killer (NK) and T cell-driven antitumor immunity, suppressed tumor growth, and improved survival of melanoma-bearing animals. Significantly higher plasma levels of antitumorigenic cytokines (TNF-α and IFN-γ), remarkably lower plasma levels of immunosuppressive cytokines (TGF-β and IL-10), and a significantly higher number of tumor-infiltrating, IFN-γ-producing, FasL- and granzyme B-expressing NK cells, IL-17-producing CD4+Th17 cells, IFN-γ- and TNF-α-producing CD4+Th1 cells, and CD8+cytotoxic T lymphocytes (CTLs) were observed in B16F10+MSC1d-treated mice. On the contrary, MSCs, injected 14 days after melanoma induction (B16F10+MSC14d-treated mice), promoted tumor growth by suppressing antigen-presenting properties of tumor-infiltrating dendritic cells (DCs) and macrophages and by reducing tumoricidal capacity of NK cells and T lymphocytes. Significantly higher plasma levels of TGF-β and IL-10, remarkably lower plasma levels of TNF-α and IFN-γ, and significantly reduced number of tumor-infiltrating, I-A-expressing, and IL-12-producing macrophages, CD80- and I-A-expressing DCs, granzyme B-expressing CTLs and NK cells, IFN-γ- and IL-17-producing CTLs, CD4+Th1, and Th17 cells were observed in B16F10+MSC14d-treated animals. In summing up, the timing of MSC administration into the tumor microenvironment was crucially important for MSC-dependent modulation of antimelanoma immunity. MSCs transplanted during the initial phase of melanoma growth exerted tumor-suppressive effect, while MSCs injected during the progressive stage of melanoma development suppressed antitumor immunity and enhanced tumor expansion.

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