Abnormal Macrophage Polarization in Patients with Myelodysplastic Syndrome

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.

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

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.

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

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.

Bone Marrow Vascular Niche: Home for Hematopoietic Stem Cells

Though discovered later than osteoblastic niche, vascular niche has been regarded as an alternative indispensable niche operating regulation on hematopoietic stem cells (HSCs). As significant progresses gained on this type niche, it is gradually clear that the main work of vascular niche is undertaking to support hematopoiesis. However, compared to what have been defined in the mechanisms through which the osteoblastic niche regulates hematopoiesis, we know less in vascular niche. In this review, based on research data hitherto we will focus on component foundation and various functions of vascular niche that guarantee the normal hematopoiesis process within bone marrow microenvironments. And the possible pathways raised by various research results through which this environment undergoes its function will be discussed as well.