Effect of NK4 Transduction in Bone Marrow-Derived Mesenchymal Stem Cells on Biological Characteristics of Pancreatic Cancer Cells

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.

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Comparison of the Biological Characteristics of Mesenchymal Stem Cells Derived from Bone Marrow and Skin

Stem Cells International ◽

10.1155/2016/3658798 ◽

2016 ◽

Vol 2016 ◽

pp. 1-12 ◽

Cited By ~ 8

Author(s):

Ruifeng Liu ◽

Wenjuan Chang ◽

Hong Wei ◽

Kaiming Zhang

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cell Types ◽

Culture Conditions ◽

Biological Characteristics ◽

Cytokine Secretion ◽

Surface Markers ◽

Tissue Repair And Regeneration

Mesenchymal stem cells (MSCs) exhibit high proliferation and self-renewal capabilities and are critical for tissue repair and regeneration during ontogenesis. They also play a role in immunomodulation. MSCs can be isolated from a variety of tissues and have many potential applications in the clinical setting. However, MSCs of different origins may possess different biological characteristics. In this study, we performed a comprehensive comparison of MSCs isolated from bone marrow and skin (BMMSCs and SMSCs, resp.), including analysis of the skin sampling area, separation method, culture conditions, primary and passage culture times, cell surface markers, multipotency, cytokine secretion, gene expression, and fibroblast-like features. The results showed that the MSCs from both sources had similar cell morphologies, surface markers, and differentiation capacities. However, the two cell types exhibited major differences in growth characteristics; the primary culture time of BMMSCs was significantly shorter than that of SMSCs, whereas the growth rate of BMMSCs was lower than that of SMSCs after passaging. Moreover, differences in gene expression and cytokine secretion profiles were observed. For example, secretion of proliferative cytokines was significantly higher for SMSCs than for BMMSCs. Our findings provide insights into the different biological functions of both cell types.

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Cancer-educated mesenchymal stem cells promote the survival of cancer cells at primary and distant metastatic sites via the expansion of bone marrow-derived-PMN-MDSCs

Cell Death and Disease ◽

10.1038/s41419-019-2149-1 ◽

2019 ◽

Vol 10 (12) ◽

Cited By ~ 2

Author(s):

Buqing Sai ◽

Yafei Dai ◽

Songqing Fan ◽

Fan Wang ◽

Lujuan Wang ◽

...

Keyword(s):

Lung Cancer ◽

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Cancer Cells ◽

Cancer Metastasis ◽

Primary Tumour ◽

Lung Cancer Cells ◽

Gm Csf ◽

Metastatic Sites

AbstractBone marrow mesenchymal stem cells (BMSCs) are multipotent stromal cells that can differentiate into a variety of cell types. BMSCs are chemotactically guided towards the cancer cells and contribute to the formation of a cancer microenvironment. The homing of BMSCs was affected by various factors. Disseminated tumour cells (DTCs) in distant organs, especially in the bone marrow, are the source of cancer metastasis and cancer relapse. DTC survival is also determined by the microenvironment. Here we aim to elucidate how cancer-educated BMSCs promote the survival of cancer cells at primary tumour sites and distant sites. We highlight the dynamic change by identifying different gene expression signatures in intratumoral BMSCs and in BMSCs that move back in the bone marrow. Intratumoral BMSCs acquire high mobility and displayed immunosuppressive effects. Intratumoral BMSCs that ultimately home to the bone marrow exhibit a strong immunosuppressive function. Cancer-educated BMSCs promote the survival of lung cancer cells via expansion of MDSCs in bone marrow, primary tumour sites and metastatic sites. These Ly6G+ MDSCs suppress proliferation of T cells. CXCL5, nitric oxide and GM-CSF produced by cancer-educated BMSCs contribute to the formation of malignant microenvironments. Treatment with CXCL5 antibody, the iNOS inhibitor 1400w and GM-CSF antibody reduced MDSC expansion in the bone marrow, primary tumour sites and metastatic sites, and promoted the efficiency of PD-L1 antibody. Our study reveals that cancer-educated BMSCs are the component of the niche for primary lung cancer cells and DTCs, and that they can be the target for immunotherapy.

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Biological Characteristics and Osteogenic Differentiation of Ovine Bone Marrow Derived Mesenchymal Stem Cells Stimulated with FGF-2 and BMP-2

International Journal of Molecular Sciences ◽

10.3390/ijms21249726 ◽

2020 ◽

Vol 21 (24) ◽

pp. 9726

Author(s):

Sandra Gromolak ◽

Agnieszka Krawczenko ◽

Agnieszka Antończyk ◽

Krzysztof Buczak ◽

Zdzisław Kiełbowicz ◽

...

Keyword(s):

Stem Cells ◽

Bone Marrow ◽

Mesenchymal Stem Cells ◽

Osteogenic Differentiation ◽

Collagen Type ◽

Collagen Type I ◽

Biological Characteristics ◽

Immunofluorescent Staining ◽

Type I ◽

Differentiation Potential

Cell-based therapies using mesenchymal stem cells (MSCs) are a promising tool in bone tissue engineering. Bone regeneration with MSCs involves a series of molecular processes leading to the activation of the osteoinductive cascade supported by bioactive factors, including fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2). In this study, we examined the biological characteristics and osteogenic differentiation potential of sheep bone marrow MSCs (BM-MSCs) treated with 20 ng/mL of FGF-2 and 100 ng/mL BMP-2 in vitro. The biological properties of osteogenic-induced BM-MSCs were investigated by assessing their morphology, proliferation, phenotype, and cytokine secretory profile. The osteogenic differentiation was characterized by Alizarin Red S staining, immunofluorescent staining of osteocalcin and collagen type I, and expression levels of genetic markers of osteogenesis. The results demonstrated that BM-MSCs treated with FGF-2 and BMP-2 maintained their primary MSC properties and improved their osteogenic differentiation capacity, as confirmed by increased expression of osteocalcin and collagen type I and upregulation of osteogenic-related gene markers BMP-2, Runx2, osterix, collagen type I, osteocalcin, and osteopontin. Furthermore, sheep BM-MSCs produced a variety of bioactive factors involved in osteogenesis, and supplementation of the culture medium with FGF-2 and BMP-2 affected the secretome profile of the cells. The results suggest that sheep osteogenic-induced BM-MSCs may be used as a cellular therapy to study bone repair in the preclinical large animal model.

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