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Bone marrow microenvironment

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https://www.readbyqxmd.com/read/28734835/migration-ability-and-toll-like-receptor-expression-of-human-mesenchymal-stem-cells-improves-significantly-after-three-dimensional-culture
#1
Panpan Zhou, Zilin Liu, Xue Li, Bing Zhang, Xiaoyuan Wang, Jing Lan, Qing Shi, Dong Li, Xiuli Ju
While the conventional two-dimensional (2D) culture protocol is well accepted for the culture of mesenchymal stem cells (MSCs), this method fails to recapitulate the in vivo native three-dimensional (3D) cellular microenvironment, and may result in phenotypic changes, and homing and migration capacity impairments. MSC preparation in 3D culture systems has been considered an attractive preparatory and delivery method recently. We seeded human umbilical cord-derived MSCs (hUCMSCs) in a 3D culture system with porcine acellular dermal matrix (PADM), and investigated the phenotypic changes, the expression changes of some important receptors, including Toll-like receptors (TLRs) and C-X-C chemokine receptor type 4 (CXCR4) when hUCMSCs were transferred from 2D to 3D systems, as well as the alterations in in vivo homing and migration potential...
July 19, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28722341/proteomic-analysis-of-neuroblastoma-derived-exosomes-new-insights-into-a-metastatic-signature
#2
Marta Colletti, Andrea Petretto, Angela Galardi, Virginia Di Paolo, Luigi Tomao, Chiara Lavarello, Elvira Inglese, Maurizio Bruschi, Ana Amor Lopez, Luisa Pascucci, Birgit Geoerger, Hector Peinado, Locatelli Franco, Di Giannatale Angela
Neuroblastoma (NB) is the most common extracranial pediatric solid tumor. Around 70% of patients with metastatic disease at diagnosis present bone-marrow infiltration, which is considered a marker of poor outcome; however, the mechanism underlying this specific tropism has to be elucidated. Tumor-derived exosomes may support metastatic progression in several tumors by interacting with the microenvironment, and may serve as tumor biomarkers. The main objective of this study was to identify an exosomal signature associated with NB metastatic bone-marrow dissemination...
July 19, 2017: Proteomics
https://www.readbyqxmd.com/read/28722316/the-mincle-ligand-trehalose-dibehenate-differentially-modulates-m1-like-and-m2-like-macrophage-phenotype-and-function-via-syk-signaling
#3
Kristel Kodar, Jacquie L Harper, Melanie J McConnell, Mattie S M Timmer, Bridget L Stocker
INTRODUCTION: Macrophages play a significant role in the progression of diseases, such as cancer, making them a target for immune-modulating agents. Trehalose dibehenate (TDB) is known to activate M1-like macrophages via Mincle, however, the effect of TDB on M2-like macrophages, which are found in the tumor microenvironment, has not been studied. METHODS: qRT-PCR, flow cytometry, cytokine ELISA, and Western Blotting were used to study the effect of TDB on GM-CSF and M-CSF/IL-4 derived bone marrow macrophages (BMMs) from C57BL/6 and Mincle(-/-) mice...
July 19, 2017: Immunity, Inflammation and Disease
https://www.readbyqxmd.com/read/28720900/low-frequency-ultrasound-induced-vegf-suppression-and-synergy-with-dendritic-cell-mediated-anti-tumor-immunity-in-murine-prostate-cancer-cells-in-vitro
#4
Wei Zhang, Wen-De Shou, Yan-Jun Xu, Wen-Kun Bai, Bing Hu
High tumor vascular endothelial growth factor (VEGF) levels are associated with poor treatment outcomes in prostate cancer (PCa), and immune deficiency in the PCa microenvironment, especially suppression of dendritic cell (DC) proliferation, has been confirmed. In this study, we (1) investigated whether VEGF participates in DC suppression in murine PCa cells (RM-1), (2) down-regulated VEGF expression using low-frequency ultrasound and microbubbles (UM), and (3) further explored any synergistic effect on immunological activation...
July 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28717423/contribution-of-neuroblastoma-derived-exosomes-to-the-production-of-pro-tumorigenic-signals-by-bone-marrow-mesenchymal-stromal-cells
#5
Rie Nakata, Hiroyuki Shimada, G Esteban Fernandez, Rob Fanter, Muller Fabbri, Jemily Malvar, Pascale Zimmermann, Yves A DeClerck
The bone marrow (BM) niche is a microenvironment promoting survival, dormancy and therapeutic resistance in tumor cells. Central to this function are mesenchymal stromal cells (MSCs). Here, using neuroblastoma (NB) as a model, we demonstrate that NB cells release an extracellular vesicle (EVs) whose protein cargo is enriched in exosomal proteins but lacks cytokines and chemokines. Using three different purification methods, we then demonstrate that NB-derived exosomes were captured by MSCs and induced the production of pro-tumorigenic cytokines and chemokines, including interleukin-6 (IL-6), IL-8/CXCL8, vascular endothelial cell growth factor and monocyte-chemotactic protein-1, with exosomes prepared by size exclusion chromatography having the highest activity...
2017: Journal of Extracellular Vesicles
https://www.readbyqxmd.com/read/28714177/curved-microstructures-promote-osteogenesis-of-mesenchymal-stem-cells-via-the-rhoa-rock-pathway
#6
Qi Zhang, Shiyu Lin, Tao Zhang, Taoran Tian, Quanquan Ma, Xueping Xie, Changyue Xue, Yunfeng Lin, Bofeng Zhu, Xiaoxiao Cai
OBJECTIVES: Cells in the osteon reside in a curved space, accordingly, the curvature of the microenvironment is an important geometric feature in bone formation. However, it is not clear how curved microstructures affect cellular behaviour in bone tissue. MATERIALS AND METHODS: Rat primary bone marrow mesenchymal stem cells (BMSCs) on wavy microgrooves were exposed to PDMS substrates with various curvatures to investigate alterations in cellular morphology and osteogenic differentiation...
August 2017: Cell Proliferation
https://www.readbyqxmd.com/read/28713366/intratumoral-lentivector-mediated-tgf-%C3%AE-1-gene-downregulation-as-a-potent-strategy-for-enhancing-the-antitumor-effect-of-therapy-composed-of-cyclophosphamide-and-dendritic-cells
#7
Joanna Rossowska, Natalia Anger, Agnieszka Szczygieł, Jagoda Mierzejewska, Elżbieta Pajtasz-Piasecka
Vaccination with dendritic cells (DCs) stimulated with tumor antigens can induce specific cellular immune response that recognizes a high spectrum of tumor antigens. However, the ability of cancer cells to produce immunosuppressive factors drastically decreases the antitumor activity of DCs. The main purpose of the study was to improve the effectiveness of DC-based immunotherapy or chemoimmunotherapy composed of cyclophosphamide (CY) and DCs by application of lentivectors (LVs)-encoding short hairpin RNA specific for TGF-β1 (shTGFβ1 LVs)...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28708600/tumor-trp53-status-and-genotype-affect-the-bone-marrow-microenvironment-in-acute-myeloid-leukemia
#8
Rodrigo Jacamo, R Eric Davis, Xiaoyang Ling, Sonali Sonnylal, Wencai Ma, Min Zhang, Peter Ruvolo, Vivian Ruvolo, Rui-Yu Wang, Scott Lowe, Johannes Zuber, Steven M Kornblau, Marina Konopleva, Michael Andreeff
The genetic heterogeneity of acute myeloid leukemia (AML) and the variable responses of individual patients to therapy suggest that different AML genotypes may influence the bone marrow (BM) microenvironment in different ways. We performed gene expression profiling of bone marrow mesenchymal stromal cells (BM-MSC) isolated from normal C57BL/6 mice or mice inoculated with syngeneic murine leukemia cells carrying different human AML genotypes, developed in mice with Trp53 wild-type or nullgenetic backgrounds...
July 6, 2017: Oncotarget
https://www.readbyqxmd.com/read/28707661/-the-effects-of-interleukin-1-beta-and-gamma-quantum-braking-radiation-on-mesenchymal-progenitor-cells
#9
A E Bigildeev, E A Zezina, N J Drize
In murine bone-marrow stromal microenvironment cells and in human multipotent mesenchymal stromal cells (MMSCs), proinflammatory cytokine interleukin-1 beta (IL-1β) serves as a growth factor. In murine bone tissue, IL-1β expression increases in vivo after irradiation. Here, we have presented our evaluation of the effects of exogenous IL-1β on the expression of NF-kB transcription factors in human MMSCs and stromal layer cells of murine long-term bone marrow cultures (LTBMCs). The cytokine signaling pathway was also activated in murine LTBMC by braking electron radiation in doses of 3-12 Gy...
May 2017: Molekuliarnaia Biologiia
https://www.readbyqxmd.com/read/28707627/mussel-inspired-nano-building-block-assemblies-for-mimicking-extracellular-matrix-microenvironments-with-multiple-functions
#10
Zhenming Wang, Zhanrong Jia, Yanan Jiang, Pengfei Li, Lu Han, Xiong Lu, Fuzeng Ren, Ke-Feng Wang, Huipin Yuan
The assembly of nano-building blocks is an effective way to produce artificial extracellular matrix microenvironments with hierarchical micro/nano structures. However, it is hard to assemble different types of nano-building blocks, to form composite coatings with multiple functions, by traditional layer-by-layer (LbL) self-assembly methods. Inspired by the mussel adhesion mechanism, we developed polydopamine (PDA)-decorated bovine serum albumin nanoparticles (BSA-NPs) and nano-hydroxyapatite (nano-HA), and assembled them to form bioactive coatings with micro/nano structures encapsulating bone morphogenetic protein-2 (BMP-2)...
July 14, 2017: Biofabrication
https://www.readbyqxmd.com/read/28688533/pathobiology-and-diagnosis-of-multiple-myeloma
#11
REVIEW
Kevin Brigle, Barbara Rogers
OBJECTIVE: To understand the role of the genetic changes and bone marrow microenvironment on the development, progression, and staging of multiple myeloma (MM). DATA SOURCES: Peer-reviewed articles and clinical guidelines. CONCLUSION: The acquisition of genetic changes and the bone marrow microenvironment in which myeloma cells develop both influence the pathogenic potential of these malignant cells and is reflected in staging of the disease, risk of progression, and predicted response to treatment...
July 5, 2017: Seminars in Oncology Nursing
https://www.readbyqxmd.com/read/28687621/cancer-associated-fibroblasts-share-characteristics-and-pro-tumorigenic-activity-with-mesenchymal-stromal-cells
#12
Lucia Borriello, Rie Nakata, Michael A Sheard, G Esteban Fernandez, Richard Sposto, Jemily Malvar, Laurence Blavier, Hiroyuki Shimada, Shahab Asgharzadeh, Robert C Seeger, Yves A DeClerck
Cancer-associated fibroblasts (CAF) have been suggested to originate from mesenchymal stromal cells (MSC), but their relationship to MSC is not clear. Here we have isolated from primary human neuroblastoma (NB) tumors a population of αFAP- and FSP-1-expressing CAF that share phenotypic and functional characteristics with bone marrow-derived MSC (BM-MSC). Analysis of human NB tumors also confirmed the presence of αFAP- and FSP-1-positive cells in the tumor stroma, and their presence correlated with that of M2 tumor-associated macrophages...
July 7, 2017: Cancer Research
https://www.readbyqxmd.com/read/28684528/wnt-%C3%A3-catenin-activation-by-epigenetically-aberrant-stroma-drives-myelodysplastic-syndrome
#13
Tushar Bhagat, Si Chen, Matthias Bartenstein, Trevor S Barlowe, Dagny von Ahrens, Gaurav S Choudhary, Patrick Tivnan, Elianna Amin, A Mario Marcondes, Mathijs A Sanders, Remco M Hoogenboezem, Suman Kambhampati, Nandini Ramachandra, Ioannis Mantzaris, Vineeth Sukrithan, Remi Laurence, Robert Lopez, Prafulla Bhagat, Orsi Giricz, Davendra Sohal, Amittha Wickrema, Cecilia Cs Yeung, Kira Gritsman, Peter D Aplan, Konrad Hochedlinger, Yiting Yu, Kith Pradhan, Jinghang Zhang, John Greally, Siddhartha Mukherjee, Andrea Pellagatti, Jacqueline Boultwood, Britta Will, Ulrich Steidl, Marc Hgp Raaijmakers, H J Deeg, Michael G Kharas, Amit Verma
The bone marrow microenvironment influences malignant hematopoiesis but how it promotes leukemogenesis has not been elucidated. Additionally, the role of the bone marrow stroma in regulating clinical responses to DNA methyltransferase inhibitors (DNMTi) is also poorly understood. In this study, we conducted a DNA methylome analysis of bone marrow-derived stromal cells from myelodysplastic syndrome (MDS) patients and observed widespread aberrant cytosine hypermethylation occurring preferentially outside CpG islands...
July 6, 2017: Cancer Research
https://www.readbyqxmd.com/read/28679949/aml-induced-osteogenic-differentiation-in-mesenchymal-stromal-cells-supports-leukemia-growth
#14
V Lokesh Battula, Phuong M Le, Jeffrey C Sun, Khoa Nguyen, Bin Yuan, Ximin Zhou, Sonali Sonnylal, Teresa McQueen, Vivian Ruvolo, Keith A Michel, Xiaoyang Ling, Rodrigo Jacamo, Elizabeth Shpall, Zhiqiang Wang, Arvind Rao, Gheath Al-Atrash, Marina Konopleva, R Eric Davis, Melvyn A Harrington, Catherine W Cahill, Carlos Bueso-Ramos, Michael Andreeff
Genotypic and phenotypic alterations in the bone marrow (BM) microenvironment, in particular in osteoprogenitor cells, have been shown to support leukemogenesis. However, it is unclear how leukemia cells alter the BM microenvironment to create a hospitable niche. Here, we report that acute myeloid leukemia (AML) cells, but not normal CD34+ or CD33+ cells, induce osteogenic differentiation in mesenchymal stromal cells (MSCs). In addition, AML cells inhibited adipogenic differentiation of MSCs. Mechanistic studies identified that AML-derived BMPs activate Smad1/5 signaling to induce osteogenic differentiation in MSCs...
July 6, 2017: JCI Insight
https://www.readbyqxmd.com/read/28677805/designer-d-form-self-assembling-peptide-scaffolds-promote-the-proliferation-and-migration-of-rat-bone-marrow-derived-mesenchymal-stem-cells
#15
Shuo Chen, Ao Zhou, Bin He, Weikang Zhao, Xiaojun Chen, Dianming Jiang
Self-assembling peptide (SAP) nanofiber hydrogel scaffolds have become increasingly important in tissue engineering due to their outstanding bioactivity and biodegradability. However, there is an initial concern on their long-term clinical use, since SAPs made of L-form amino acid sequences are sensitive to enzymatic degradation. In this study, we present a designer SAP, D-RADA16, made of all D-amino acid. We investigated the nanofiber morphology of D-RADA16, its potential for the culture of bone marrow-derived mesenchymal stem cells (BMSCs), and the proteolytic resistance of the biomaterial...
July 5, 2017: International Journal of Molecular Medicine
https://www.readbyqxmd.com/read/28677743/yi-guan-jian-decoction-may-enhance-hepatic-differentiation-of-bone-marrow%C3%A2-derived-mesenchymal-stem-cells-via-sdf%C3%A2-1-in%C3%A2-vitro
#16
Lin-Lin Fu, Bing-Yao Pang, Ying Zhu, Ling Wang, Ai-Jing Leng, Hai-Long Chen
A previous study reported that Yi Guan Jian (YGJ) may increase the proliferation and differentiation of hepatic oval cells in a rat liver cirrhosis model. The aim of the present study was to investigate the effect and mechanism of action of YGJ on inducing hepatic differentiation in bone marrow‑derived mesenchymal stem cells (BM‑MSCs) via stromal‑cell derived factor‑1 (SDF‑1). Murine BM‑MSCs were isolated with whole bone marrow adherence, then identified by immunocytochemical staining and flow cytometry...
June 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28677723/telomere-length-is-positively-associated-with-the-expression-of-il%C3%A2-6-and-mip%C3%A2-1%C3%AE-in-bone-marrow-mesenchymal-stem-cells-of-multiple-myeloma
#17
Shengli Li, Yang Jiang, Ai Li, Xiaoli Liu, Xiangling Xing, Yanan Guo, Yaqi Xu, Yunliang Hao, Chengyun Zheng
Potential roles of mesenchymal stem cells (MSCs) in the pathogenesis of multiple myeloma (MM) are largely unknown. In the current study, the authors analyzed telomere length and the expressions of interleukin (IL)‑6 and macrophage inflammatory protein (MIP)‑1α in MSCs derived from the bone marrow (BM) of MM patients and controls. The current results demonstrated that there was no significant difference in cell surface expression of CD73 and CD90, and the capacity to differentiate into bone tissue were identified between the BM MSCs derived from MM patients and controls...
June 29, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28675788/proteomics-profiling-of-exosomes-from-primary-mouse-osteoblasts-under-proliferation-versus-mineralization-conditions-and-characterization-of-their-uptake-into-prostate-cancer-cells
#18
Mehmet Asim Bilen, Tianhong Pan, Yu-Chen Lee, Song-Chang Lin, Guoyu Yu, Jing Pan, David H Hawke, Bih-Fang Pan, Jody Vykoukal, Kavanya Gray, Robert L Satcher, Gary E Gallick, Li-Yuan Yu-Lee, Sue-Hwa Lin
Osteoblasts communicate both with normal cells in the bone marrow, and with tumor cells that metastasized to bone. Here we show that osteoblasts release exosomes, we termed osteosomes, which may be a novel mechanism by which osteoblasts communicate with cells in their environment. We have isolated exosomes from undifferentiated/proliferating (D0 osteosomes) and differentiated/mineralizing (D24 osteosomes) primary mouse calvarial osteoblasts. The D0 and D24 osteosomes were found to be vesicles of 130-140 nm by dynamic light scattering analysis...
July 4, 2017: Journal of Proteome Research
https://www.readbyqxmd.com/read/28675022/-tumor-necrosis-factor-%C3%AE-regulates-the-osteogenic-differentiation-of-bone-marrow-mesenchymal-stem-cells-in-chronic-periodontitis
#19
Li Xiaoguang, Wang Yizhu, Guo Bin
Bone marrow mesenchymal stem cells (BMSCs) and ideal adult stem cells for alveolar bone regeneration considerably help restore the structure and function of the periodontium and promote the healing of periodontal disease. Thus, BMSC features, especially the mechanism of osteogenic differentiation, has recently become a research hotspot. Tumor necrosis factor-α (TNF-α), which is the main factor in the periodontal inflammatory microenvironment, is directly related to the osteogenic differentiation of BMSCs...
June 1, 2017: Hua Xi Kou Qiang Yi Xue za Zhi, Huaxi Kouqiang Yixue Zazhi, West China Journal of Stomatology
https://www.readbyqxmd.com/read/28673395/mechanisms-of-resistance-to-flt3-inhibitors-and-the-role-of-the-bone-marrow-microenvironment
#20
REVIEW
Gabriel Ghiaur, Mark Levis
The presence of FLT3 mutations in acute myeloid leukemia (AML) carries a particularly poor prognosis, making the development of FLT3 inhibitors an imperative goal. The last decade has seen an abundance of clinical trials using these drugs alone or in combination with chemotherapy. This culminated with the recent approval by the US Food and Drug Administration of Midostaurin for the treatment of FLT3-mutated AML. Initial success has been followed by the emergence of clinical resistance. Although novel FLT3 inhibitors are being developed, studies into mechanisms of resistance raise hope of new strategies to prevent emergence of resistance and eliminate minimal residual disease...
August 2017: Hematology/oncology Clinics of North America
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