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https://www.readbyqxmd.com/read/28099937/inactivation-of-ck1%C3%AE-in-multiple-myeloma-empowers-drug-cytotoxicity-by-affecting-akt-and-%C3%AE-catenin-survival-signaling-pathways
#1
Sabrina Manni, Marilena Carrino, Martina Manzoni, Ketty Gianesin, Sara Canovas Nunes, Matteo Costacurta, Laura Quotti Tubi, Paolo Macaccaro, Elisa Taiana, Anna Cabrelle, Gregorio Barilà, Annalisa Martines, Renato Zambello, Laura Bonaldi, Livio Trentin, Antonino Neri, Gianpietro Semenzato, Francesco Piazza
Recent evidence indicates that protein kinase CK1α may support the growth of multiple myeloma (MM) plasma cells. Here, by analyzing a large cohort of MM cases, we found that high CK1α mRNA levels are virtually associated with all MM patients. Moreover, we provided functional evidence that CK1α activity is essential for malignant plasma cell survival even in the protective niche generated by co-cultures with bone marrow stromal cells. We demonstrated that CK1α inactivation, while toxic for myeloma cells, is dispensable for the survival of healthy B lymphocytes and stromal cells...
January 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28098778/bone-niches-hematopoietic-stem-cells-and-vessel-formation
#2
REVIEW
Roberto Tamma, Domenico Ribatti
Bone marrow (BM) is a source of hematopoietic stem cells (HSCs). HSCs are localized in both the endosteum, in the so-called endosteal niche, and close to thin-walled and fenestrated sinusoidal vessel in the center of BM, in the so-called vascular niche. HSCs give rise to all types of mature blood cells through a process finely controlled by numerous signals emerging from the bone marrow niches where HSCs reside. This review will focus on the description of the role of BM niches in the control of the fate of HSCs and will also highlight the role of the BM niches in the regulation of vasculogenesis and angiogenesis...
January 13, 2017: International Journal of Molecular Sciences
https://www.readbyqxmd.com/read/28092776/periosteum-tissue-engineering-in-an-orthotopic-in%C3%A2-vivo-platform
#3
J G Baldwin, F Wagner, L C Martine, B M Holzapfel, C Theodoropoulos, O Bas, F M Savi, C Werner, E M De-Juan-Pardo, D W Hutmacher
The periosteum plays a critical role in bone homeostasis and regeneration. It contains a vascular component that provides vital blood supply to the cortical bone and an osteogenic niche that acts as a source of bone-forming cells. Periosteal grafts have shown promise in the regeneration of critical size defects, however their limited availability restricts their widespread clinical application. Only a small number of tissue-engineered periosteum constructs (TEPCs) have been reported in the literature. A current challenge in the development of appropriate TEPCs is a lack of pre-clinical models in which they can reliably be evaluated...
November 20, 2016: Biomaterials
https://www.readbyqxmd.com/read/28092074/biomimetic-coprecipitation-of-silk-fibrin-and-calcium-phosphate-influence-of-selenite-ions
#4
Yanhua Wang, Hang Hao, Shengmin Zhang
Large bone defect creates an urgent need for osteogenic biomaterials. However, bone nonunion and infection are choke points in the therapy of this disease. How to recruit the mesenchymal stem cells to defect sites and increase the cell viability are the critical processes. One effective method was the fabrication of biomimetic silk fibrin/selenium-doped hydroxyapatite (SF/HASe) material, which could create a niche for cell proliferation. So, the aim of the present study was to seek a facile route to prepare this biocomposites and investigate the osteogenic capability...
January 14, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28077677/pharmacological-rescue-of-diabetic-skeletal-stem-cell-niches
#5
Ruth Tevlin, Eun Young Seo, Owen Marecic, Adrian McArdle, Xinming Tong, Bryan Zimdahl, Andrey Malkovskiy, Rahul Sinha, Gunsagar Gulati, Xiyan Li, Taylor Wearda, Rachel Morganti, Michael Lopez, Ryan C Ransom, Christopher R Duldulao, Melanie Rodrigues, Allison Nguyen, Michael Januszyk, Zeshaan Maan, Kevin Paik, Kshemendra-Senarath Yapa, Jayakumar Rajadas, Derrick C Wan, Geoffrey C Gurtner, Michael Snyder, Philip A Beachy, Fan Yang, Stuart B Goodman, Irving L Weissman, Charles K F Chan, Michael T Longaker
Diabetes mellitus (DM) is a metabolic disease frequently associated with impaired bone healing. Despite its increasing prevalence worldwide, the molecular etiology of DM-linked skeletal complications remains poorly defined. Using advanced stem cell characterization techniques, we analyzed intrinsic and extrinsic determinants of mouse skeletal stem cell (mSSC) function to identify specific mSSC niche-related abnormalities that could impair skeletal repair in diabetic (Db) mice. We discovered that high serum concentrations of tumor necrosis factor-α directly repressed the expression of Indian hedgehog (Ihh) in mSSCs and in their downstream skeletogenic progenitors in Db mice...
January 11, 2017: Science Translational Medicine
https://www.readbyqxmd.com/read/28070554/marrow-inspired-matrix-cues-rapidly-affect-early-fate-decisions-of-hematopoietic-stem-and-progenitor-cells
#6
Ji Sun Choi, Brendan A C Harley
Hematopoiesis is the physiological process where hematopoietic stem cells (HSCs) continuously generate the body's complement of blood and immune cells within unique regions of the bone marrow termed niches. Although previous investigations have revealed gradients in cellular and extracellular matrix (ECM) content across the marrow, and matrix elasticity and ligand type are believed to be strong regulators of stem cell fate, the impact of biophysical signals on HSC response is poorly understood. Using marrow-inspired ECM ligand-coated polyacrylamide substrates that present defined stiffness and matrix ligand cues, we demonstrate that the interplay between integrin engagement and myosin II activation processes affects the morphology, proliferation, and myeloid lineage specification of primary murine HSCs within 24 hours ex vivo...
January 2017: Science Advances
https://www.readbyqxmd.com/read/28068876/tissue-engineered-model-of-human-osteolytic-bone-tumor
#7
Aranzazu Villasante, Alessandro Marturano, Samuel T Robinson, Zen Liu, X Edward Guo, Gordana Vunjak-Novakovic
Ewing's sarcoma (ES) is a poorly differentiated pediatric tumor of aggressive behavior characterized by propensity to metastasize to bone. Interactions between the tumor and bone cells orchestrate a vicious cycle in which tumor cells induce osteoclast differentiation and activation to cause osteolytic lesions, broken bones, pain and hypercalcemia. The lack of controllable models that can recapitulate osteolysis in ES impedes the development of new therapies and limits our understanding of how tumor cells invade bone...
January 9, 2017: Tissue Engineering. Part C, Methods
https://www.readbyqxmd.com/read/28068081/peptide-decorated-nanofibrous-niche-augments-in-vitro-directed-osteogenic-conversion-of-human-pluripotent-stem-cells
#8
Yi Deng, Yuanyi Yang, Shicheng Wei
Realization of clinical potential of human pluripotent stem cells (hPSCs) in bone regenerative medicine requires development of simple and safe biomaterials for expansion of hPSCs followed by directing their lineage commitment to osteoblasts. In the present study, a chemically defined peptide-decorated polycaprolactone (PCL) nanofibrous microenvironment was prepared through electrospinning technology and subsequent conjugation with vitronectin peptide to promote the culture and osteogenic potential of hPSCs in vitro...
January 9, 2017: Biomacromolecules
https://www.readbyqxmd.com/read/28067666/versatile-humanized-niche-model-enables-study-of-normal-and-malignant-human-hematopoiesis
#9
Ander Abarrategi, Katie Foster, Ashley Hamilton, Syed A Mian, Diana Passaro, John Gribben, Ghulam Mufti, Dominique Bonnet
The BM niche comprises a tightly controlled microenvironment formed by specific tissue and cells that regulates the behavior of hematopoietic stem cells (HSCs). Here, we have provided a 3D model that is tunable in different BM niche components and useful, both in vitro and in vivo, for studying the maintenance of normal and malignant hematopoiesis. Using scaffolds, we tested the capacity of different stromal cell types to support human HSCs. Scaffolds coated with human mesenchymal stromal cells (hMSCs) proved to be superior in terms of HSC engraftment and long-term maintenance when implanted in vivo...
January 9, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28064238/myeloid-malignancies-and-the-microenvironment
#10
Claudia Korn, Simón Méndez-Ferrer
Research in the last few years has revealed a sophisticated interaction network between multiple bone marrow (BM) cells that regulate different hematopoietic stem cell (HSC) properties, such as proliferation, differentiation, localization and self-renewal during homeostasis. These mechanisms are essential to keep the physiological HSC numbers in check and interfere with malignant progression. Besides the identification of multiple mutations and chromosomal aberrations driving the progression of myeloid malignancies, alterations in the niche compartment recently gained attention in contributing to disease progression...
November 15, 2016: Blood
https://www.readbyqxmd.com/read/28062525/parathyroid-hormone-1-34-and-skeletal-anabolic-action-the-use-of-parathyroid-hormone-in-bone-formation
#11
L Osagie-Clouard, A Sanghani, M Coathup, T Briggs, M Bostrom, G Blunn
: Intermittently administered parathyroid hormone (PTH 1-34) has been shown to promote bone formation in both human and animal studies. The hormone and its analogues stimulate both bone formation and resorption, and as such at low doses are now in clinical use for the treatment of severe osteoporosis. By varying the duration of exposure, parathyroid hormone can modulate genes leading to increased bone formation within a so-called 'anabolic window'. The osteogenic mechanisms involved are multiple, affecting the stimulation of osteoprogenitor cells, osteoblasts, osteocytes and the stem cell niche, and ultimately leading to increased osteoblast activation, reduced osteoblast apoptosis, upregulation of Wnt/β-catenin signalling, increased stem cell mobilisation, and mediation of the RANKL/OPG pathway...
January 2017: Bone & Joint Research
https://www.readbyqxmd.com/read/28043948/angptl2-expression-in-the-intestinal-stem-cell-niche-controls-epithelial-regeneration-and-homeostasis
#12
Haruki Horiguchi, Motoyoshi Endo, Kohki Kawane, Tsuyoshi Kadomatsu, Kazutoyo Terada, Jun Morinaga, Kimi Araki, Keishi Miyata, Yuichi Oike
The intestinal epithelium continually self-renews and can rapidly regenerate after damage. Dysregulation of intestinal epithelial homeostasis leads to severe inflammatory bowel disease. Additionally, aberrant signaling by the secreted protein angiopoietin-like protein 2 (ANGPTL2) causes chronic inflammation in a variety of diseases. However, little is known about the physiologic role of ANGPTL2 in normal tissue homeostasis and during wound repair following injury. Here, we assessed ANGPTL2 function in intestinal physiology and disease in vivo Although intestinal development proceeded normally in Angptl2-deficient mice, expression levels of the intestinal stem cell (ISC) marker gene Lgr5 decreased, which was associated with decreased transcriptional activity of β-catenin in Angptl2-deficient mice...
January 2, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28031339/staphylococcus-aureus-protein-a-disrupts-immunity-mediated-by-long-lived-plasma-cells
#13
Amanda B Keener, Lance T Thurlow, SunAh Kang, Nicholas A Spidale, Stephen H Clarke, Kenji M Cunnion, Roland Tisch, Anthony R Richardson, Barbara J Vilen
Infection with Staphylococcus aureus does not induce long-lived protective immunity for reasons that are not completely understood. Human and murine vaccine studies support a role for Abs in protecting against recurring infections, but S. aureus modulates the B cell response through expression of staphylococcus protein A (SpA), a surface protein that drives polyclonal B cell expansion and induces cell death in the absence of costimulation. In this murine study, we show that SpA altered the fate of plasmablasts and plasma cells (PCs) by enhancing the short-lived extrafollicular response and reducing the pool of bone marrow (BM)-resident long-lived PCs...
December 28, 2016: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28031234/the-multiple-roles-of-exosomes-in-metastasis
#14
REVIEW
Ulrich H Weidle, Fabian Birzele, Gwen Kollmorgen, Rüdiger Rüger
Exosomes are important contributors to cell-cell communication and their role as diagnostic markers for cancer and the pathogenesis for cancer is under intensive investigation. Here, we focus on their role in metastasis-related processes. We discuss their impact regarding promotion of invasion and migration of tumor cells, conditioning of lymph nodes, generation of premetastatic niches and organotropism of metastasis. Furthermore, we highlight interactions of exosomes with bone marrow and stromal components such as fibroblasts, endothelial cells, myeloid- and other immune-related cells in the context of metastases...
2, 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28028233/aberrantly-expressed-lgr4-empowers-wnt-signaling-in-multiple-myeloma-by-hijacking-osteoblast-derived-r-spondins
#15
Harmen van Andel, Zemin Ren, Iris Koopmans, Sander P J Joosten, Kinga A Kocemba, Wim de Lau, Marie José Kersten, Alexander M de Bruin, Jeroen E J Guikema, Hans Clevers, Marcel Spaargaren, Steven T Pals
The unrestrained growth of tumor cells is generally attributed to mutations in essential growth control genes, but tumor cells are also affected by, or even addicted to, signals from the microenvironment. As therapeutic targets, these extrinsic signals may be equally significant as mutated oncogenes. In multiple myeloma (MM), a plasma cell malignancy, most tumors display hallmarks of active Wnt signaling but lack activating Wnt-pathway mutations, suggesting activation by autocrine Wnt ligands and/or paracrine Wnts emanating from the bone marrow (BM) niche...
December 27, 2016: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28026131/sphingosine-1-phosphate-receptor-3-supports-hematopoietic-stem-and-progenitor-cell-residence-within-the-bone-marrow-niche
#16
Molly E Ogle, Claire E Olingy, Anthony O Awojoodu, Anusuya Das, Rafael A Ortiz, Hoi Yin Cheung, Edward A Botchwey
Hematopoietic stem and progenitor cells (HSPCs) egress from bone marrow (BM) during homeostasis and at increased rates during stress; however, the mechanisms regulating their trafficking remain incompletely understood. Here we describe a novel role for lipid receptor, sphingosine-1-phosphate receptor 3 (S1PR3), in HSPC residence within the BM niche. HSPCs expressed increased levels of S1PR3 compared to differentiated BM cells. Pharmacological antagonism or knockout (KO) of S1PR3 mobilized HSPCs into blood circulation, suggesting that S1PR3 influences niche localization...
December 27, 2016: Stem Cells
https://www.readbyqxmd.com/read/28024508/-reconstruction-of-humanized-bone-marrow-niche-in-immunodeficiency-mouse
#17
Huan Chen, Zheng Tian, Bin Li, Hai-Yan Xing, Huan Li, Ke-Jing Tang, Min Wang, Qing Rao
OBJECTIVE: To reconstruct a human bone marrow niche in immunodeficiency mouse (NOD/SCID) so as to provide a model for observing the effect of abnormal BM niche on the occurence and development of leukemia. METHODS: Human platelet lysate(HPL) was obtained by repeated freezing and thawing of concentrated platelet. Bone marrow-derived mesenchymal stem cells were cultured in α-minimal essential medium (α-MEM) containing 10% HPL or 10% FBS. The morphology, cell phenotype, multilineage differentiation potential in vitro and proliferation capacity between the mesenchymal stem cells cultured with HPL or FBS were compared...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28024466/-role-of-nf-%C3%AE%C2%BAb-inhibitor-in-acute-myeloid-leukemia
#18
Wei-Li Wang, Qiao-Zhu Xu, Xiao-Huan Mu, Le Wang, Li-Yan Zhang, Jing Xu, Ying-Dai Gao, Tao Cheng, Wei-Ping Yuan
OBJECTIVE: To investigate the role of NF-κB inhibitor in occurence and development of AML. METHODS: AML and normal bone marrow samples were collected from 8 AML patients and 8 normal persons. The expression of NF-κB signaling pathway genes was detected by NF-κB PCR array. Then, AML mouse model was constructed to test the role of NF-κB inhibitor in AML. RESULTS: The NF-κB signal pathway was activated in AML patients. The up-regulated genes, EDARADD, TNFSF14, could activate the NF-κB signal pathway, IL6 could regulate the inflammatory signal...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28017869/endosteal-like-extracellular-matrix-expression-on-melt-electrospun-written-scaffolds
#19
Maria Lourdes Muerza-Cascante, Ali Shokoohmand, Kiarash Khosrotehrani, David Haylock, Paul D Dalton, Dietmar W Hutmacher, Daniela Loessner
: Tissue engineering technology platforms constitute a unique opportunity to integrate cells and extracellular matrix (ECM) proteins into scaffolds and matrices that mimic the natural microenvironments in vitro. The developments of tissue-engineered 3D models that mimic the endosteal microenvironment enable researchers to discover the causes and improve treatments for blood and immune-related diseases. The aim of this study was to establish a physiologically relevant in vitro model using 3D printed scaffolds to assess the contribution of human cells to the formation of a construct that mimics human endosteum...
December 22, 2016: Acta Biomaterialia
https://www.readbyqxmd.com/read/28009288/engineered-murine-hscs-reconstitute-multi-lineage-hematopoiesis-and-adaptive-immunity
#20
Yi-Fen Lu, Patrick Cahan, Samantha Ross, Julie Sahalie, Patricia M Sousa, Brandon K Hadland, Wenqing Cai, Erik Serrao, Alan N Engelman, Irwin D Bernstein, George Q Daley
Hematopoietic stem cell (HSC) transplantation is curative for malignant and genetic blood disorders, but is limited by donor availability and immune-mismatch. Deriving HSCs from patient-matched embryonic/induced-pluripotent stem cells (ESCs/iPSCs) could address these limitations. Prior efforts in murine models exploited ectopic HoxB4 expression to drive self-renewal and enable multi-lineage reconstitution, yet fell short in delivering robust lymphoid engraftment. Here, by titrating exposure of HoxB4-ESC-HSC to Notch ligands, we report derivation of engineered HSCs that self-renew, repopulate multi-lineage hematopoiesis in primary and secondary engrafted mice, and endow adaptive immunity in immune-deficient recipients...
December 20, 2016: Cell Reports
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