scholarly journals Bioengineering of Humanized Bone Marrow Microenvironments in Mouse and Their Visualization by Live Imaging

10.3791/55914 ◽  
2017 ◽  
Author(s):  
Diana Passaro ◽  
Ander Abarrategi ◽  
Katie Foster ◽  
Linda Ariza-McNaughton ◽  
Dominique Bonnet
Keyword(s):  
Bone Marrow ◽  
Live Imaging ◽  
Bone Marrow Microenvironments

scholarly journals Abnormal Macrophage Polarization in Patients with Myelodysplastic Syndrome

2021 ◽  
Vol 2021 ◽  
pp. 1-8
Author(s):  
Gaochao Zhang ◽  
Liyan Yang ◽  
Yu Han ◽  
Haiyue Niu ◽  
Li Yan ◽  
...  
Keyword(s):  
Bone Marrow ◽  
Myelodysplastic Syndrome ◽  
Macrophage Polarization ◽  
Control Group ◽  
M2 Macrophages ◽  
M1 Macrophages ◽  
Tnf Α ◽  
Bone Marrow Microenvironments ◽  
Medical University

Background. This study is aimed at assessing the subsets of bone marrow macrophages in patients with myelodysplastic syndrome (MDS) and exploring the role of macrophages in the pathogenesis of MDS. Methods. Thirty-eight newly diagnosed MDS patients were enrolled in the Department of Hematology of General Hospital of Tianjin Medical University from June 2015 to June 2016. Bone marrow monocytes and macrophage subsets (M1/M2) were detected in patients with MDS and normal controls by flow cytometry. M1 macrophages were cultured in vitro, and the expression of IL-1β and TNF-α mRNA was measured using real-time polymerase chain reaction. Results. Compared with the normal control group, the proportion of bone marrow monocytes was higher ( 2.11 ± 0.93 % vs. 3.66 ± 3.38 % ), and the mean fluorescence intensity of surface molecule CD14 was lower in the higher-risk (HR) MDS group ( 639.05 ± 359.78 vs. 458.26 ± 306.72 , p < 0.05 ). The ratio of M2 macrophages to monocytes was higher in patients with HR-MDS ( 1.82 ± 2.47 % vs. 3.93 ± 3.81 % , p < 0.05 ). The ratio of M1 to M2 macrophages was lower in the HR-MDS group ( 3.50 ± 3.22 vs. 1.80 ± 0.88 , p < 0.05 ). The expression of IL-1β and TNF-α mRNA in M1 macrophages was significantly lower in the MDS group ( p < 0.05 ). Conclusions. Patients with MDS had abnormal macrophage polarization, which may be involved in the alteration of bone marrow microenvironments.

scholarly journals T-cell acute leukaemia exhibits dynamic interactions with bone marrow microenvironments

Nature ◽  
2016 ◽  
Vol 538 (7626) ◽  
pp. 518-522 ◽  
Author(s):  
Edwin D. Hawkins ◽  
Delfim Duarte ◽  
Olufolake Akinduro ◽  
Reema A. Khorshed ◽  
Diana Passaro ◽  
...  
Keyword(s):  
Bone Marrow ◽  
T Cell ◽  
Acute Leukaemia ◽  
Dynamic Interactions ◽  
Bone Marrow Microenvironments

scholarly journals Effects of the Bone/Bone Marrow Microenvironments on Prostate Cancer Cells and CD59 Expression

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Bo Yan ◽  
Yan Li ◽  
Shaoju Min ◽  
Peng Zhang ◽  
Bin Xu ◽  
...  
Keyword(s):  
Prostate Cancer ◽  
Cell Cycle ◽  
Bone Marrow ◽  
Cyclin D1 ◽  
Cancer Cells ◽  
Migration And Invasion ◽  
Cell Cycle Distribution ◽  
Prostate Cancer Cells ◽  
Pc3 Cells ◽  
Bone Marrow Microenvironments

Objective. To evaluate the effects of human bone marrow mesenchymal stem cells (hBMSCs) and osteoblasts (hFOB1.19) on PC3 prostate cancer cells. Methods. To simulate the in vivo interaction between the bone/bone marrow microenvironments and prostate cancer cells, we established cocultures of PC3 cells with hBMSC or hFOB1.19 cells and evaluated their effects on the proliferation, cell cycle distribution, cell migration, and invasion of PC3 cells. Quantitative reverse transcription polymerase chain reaction was used to detect CD59 mRNA expression in PC3 cells. The expression of receptor activator of nuclear factor- (NF-) κB (RANK), RANK ligand (RANKL), osteoprotegerin (OPG), CD59, NF-κB (p50 subunit), and cyclin D1 in PC3 cells was analyzed by immunofluorescence and western blotting. Results. hBMSCs and hFOB1.19 cells enhanced the proliferation, migration, and invasion of PC3 cells; increased the proportion of PC3 cells in the S and G2/M phases of the cell cycle; and upregulated RANK, RANKL, OPG, CD59, cyclin D1, and NF-κB (p50 subunit) expression by PC3 cells. The RANKL inhibitor, scutellarin, inhibited these effects in PC3-hFOB1.19 cocultures. Conclusion. hBMSCs and hFOB1.19 cells modulate the phenotype of PC3 prostate cancer cells and the expression of CD59 by activating the RANK/RANKL/OPG signaling pathway.

scholarly journals 3D Models of Surrogate Multiple Myeloma Bone Marrow Microenvironments: Insights on Disease Pathophysiology and Patient-Specific Response to Drugs

2021 ◽  
Author(s):  
Marina Ferrarini ◽  
Magda Marcatti ◽  
Fabio Ciceri ◽  
Elisabetta Ferrero
Keyword(s):  
Multiple Myeloma ◽  
Bone Marrow ◽  
Ex Vivo ◽  
Critical Role ◽  
3D Models ◽  
Preclinical Models ◽  
Patient Will ◽  
Potential Applications ◽  
Bone Marrow Microenvironments

Multiple Myeloma (MM) develops almost exclusively within the Bone Marrow (BM), highlighting the critical role of the microenvironment in conditioning disease progression and resistance to drugs. Indeed, while the therapeutic armamentarium for MM has significantly improved over the past 20 years, the disease remains ultimately incurable. This failure may depend on the high phenotypic and genetic heterogeneity of MM, but also on the paucity and inadequacy of two-dimensional (2D) conventional preclinical models in reproducing MM within the BM. In the present paper, we provide a brief updated overview on MM BM microenvironment. We then discuss newly developed preclinical models mimicking MM/microenvironment interactions, including three-dimensional (3D), gel-based, in vitro models and a novel ex vivo system of isolated tumor and stromal cells cultured in bioreactor. Potential applications of each model, relative to investigation of MM pathogenic mechanisms and prediction of the best drug/combination for each individual patient will be also evaluated.

FAK Regulates Progenitor B Cell Growth, Localization and Retention in Bone Marrow Microenvironments

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1119-1119
Author(s):  
Shin-Young Park ◽  
Peter Wolfram ◽  
John Manis ◽  
Hilary Beggs ◽  
Cesar Nombela-Arrieta ◽  
...  
Keyword(s):  
Bone Marrow ◽  
B Cells ◽  
B Cell ◽  
Laser Scanning ◽  
Conflicts Of Interest ◽  
Ex Vivo ◽  
Wild Type ◽  
Gradient Distribution ◽  
Bone Marrow Microenvironments ◽  
B Cell Homeostasis

Abstract Abstract 1119 Progenitor B cells are thought to reside in complex bone marrow microenvironments, e.g. niches, where they receive signals for growth and maturation. Here we have conditionally targeted in B cells the non-receptor tyrosine kinase, Focal Adhesion Kinase (FAK), because of its function as an integrator of cell extrinsic signals including CXCL12 and VCAM-1. The number of progenitor (pro-, pre- and immature) B cells is reduced by 30–40% in CD19-Cre Fak fl/fl mice compared to wild type mice, and ex vivo cultured, Fak deleted pro-B cells exhibit impaired IL-7 ± CXCL12 mediated proliferation and survival. A novel quantitative laser scanning cytometry approach was used to demonstrate that Fak deletion also disrupts the non-random gradient distribution in femoral bone marrow of progenitor B cells, which normally are preferentially localized in endosteal regions of the metaphyses and to a lesser degree of the diaphysis. Increased numbers of pro-B cells are detected in the periphery of Fak deleted mice, and mobilization of pro-B cells induced by the inflammatory antigen NP-CGG-alum is increased 3-fold in Fak-deleted versus wild type mice. In addition, intravenously transferred Fak deleted pro-B cells have defective homing specifically to the extra-vascular compartment of the bone marrow. Collectively, these studies illustrate the importance of FAK in regulating progenitor B cell homeostasis and maintenance of their spatial distribution in bone marrow niches. Disclosures: No relevant conflicts of interest to declare.

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