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Bone niche

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https://www.readbyqxmd.com/read/28319565/bone-marrow-graft-versus-host-disease-in-major-histocompatibility-complex-matched-murine-reduced-intensity-allogeneic-hemopoietic-cell-transplantation
#1
Kifah Shahin, Zamil Mattar, Pablo Silveira, Wei-Hsun Hsu, Linda Bendall, Derek Hart, Kenneth F Bradstock
BACKGROUND: Most clinical allogeneic hemopoietic cell transplants (alloHCT) are now performed using reduced intensity conditioning (RIC) instead of myeloablative (MAC) conditioning, however, the biology underlying this treatment remains incompletely understood. METHODS: We investigated a murine model of major histocompatibility complex (MHC)-matched multiple minor histocompatibility antigen mismatched alloHCT, using bone marrow (BM) cells and splenocytes from B6 (H-2) donor mice transplanted into BALB...
March 18, 2017: Transplantation
https://www.readbyqxmd.com/read/28319044/fibroblastic-niches-prime-t-cell-alloimmunity-through-delta-like-notch-ligands
#2
Jooho Chung, Christen L Ebens, Eric Perkey, Vedran Radojcic, Ute Koch, Leonardo Scarpellino, Alexander Tong, Frederick Allen, Sherri Wood, Jiane Feng, Ann Friedman, David Granadier, Ivy T Tran, Qian Chai, Lucas Onder, Minhong Yan, Pavan Reddy, Bruce R Blazar, Alex Y Huang, Todd V Brennan, D Keith Bishop, Burkhard Ludewig, Christian W Siebel, Freddy Radtke, Sanjiv A Luther, Ivan Maillard
Alloimmune T cell responses induce graft-versus-host disease (GVHD), a serious complication of allogeneic bone marrow transplantation (allo-BMT). Although Notch signaling mediated by Delta-like 1/4 (DLL1/4) Notch ligands has emerged as a major regulator of GVHD pathogenesis, little is known about the timing of essential Notch signals and the cellular source of Notch ligands after allo-BMT. Here, we have shown that critical DLL1/4-mediated Notch signals are delivered to donor T cells during a short 48-hour window after transplantation in a mouse allo-BMT model...
March 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28318761/the-bone-marrow-microenvironment-home-of-the-leukemic-blasts
#3
REVIEW
Manar S Shafat, Bruno Gnaneswaran, Kristian M Bowles, Stuart A Rushworth
Acute Myeloid Leukaemia (AML) is a genetically, biologically and clinically heterogeneous set of diseases, which are characterised by an increased growth of abnormal myeloid progenitor cells within the bone marrow (BM). Ex-vivo AML exhibits a high level of spontaneous apoptosis. Furthermore, relapse for patients achieving remission occurs from minimal residual disease harboured within the BM microenvironment. Taken together, these observations illustrate the importance of the BM microenvironment in sustaining AML...
March 12, 2017: Blood Reviews
https://www.readbyqxmd.com/read/28316120/synergistic-effects-of-g-csf-and-bone-marrow-stromal-cells-on-nerve-regeneration-with-acellular-nerve-xenografts
#4
Hua Jia, Ying Wang, Tao Wang, Yi Dong, Wei-Li Li, Jun-Ping Li, Wen-Zhi Ma, Xiao-Jie Tong, Zhong-Yi He
Peripheral nerve defects result in severe denervation presenting sensory and motor functional incapacitation. Currently, a satisfactory therapeutic treatment promoting the repair of injured nerves is not available. As shown in our previous study, acellular nerve xenografts (ANX) implanted with bone marrow stromal cells (BMSCs) replaced allografts and promoted nerve regeneration. Additionally, granulocyte-colony stimulating factor (G-CSF) has been proven to mobilize supplemental cells and enhance vascularization in the niche...
March 18, 2017: Synapse
https://www.readbyqxmd.com/read/28303517/vascular-and-perivascular-niches-but-not-the-osteoblastic-niche-are-numerically-restored-following-allogeneic-hematopoietic-stem-cell-transplantation-in-patients-with-aplastic-anemia
#5
Liangliang Wu, Wenjian Mo, Yuping Zhang, Ming Zhou, Yumiao Li, Ruiqing Zhou, Shiling Xu, Shiyi Pan, Hui Deng, Ping Mao, Shunqing Wang
Bone marrow (BM) niches, including the osteoblastic, vascular, and perivascular niches, are numerically impaired in patients with aplastic anemia (AA). It remains unclear whether these niches are numerically restored in AA patients after allogenic hematopoietic stem cell transplantation (allo-HSCT). To investigate changes in BM niches, we monitored 52 patients with AA who had undergone allo-HSCT and performed immunohistochemical studies of BM niches using antibodies against CD34, CD146, and osteopontin. After allo-HSCT, patients with AA exhibited a remarkable increase in the number of cellular elements in the BM niches, including the vascular and perivascular cells...
March 16, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28297579/endothelial-cells-promote-expansion-of-long-term-engrafting-marrow-hematopoietic-stem-and-progenitor-cells-in-primates
#6
Jennifer L Gori, Jason M Butler, Balvir Kunar, Michael G Poulos, Michael Ginsberg, Daniel J Nolan, Zachary K Norgaard, Jennifer E Adair, Shahin Rafii, Hans-Peter Kiem
Successful expansion of bone marrow (BM) hematopoietic stem and progenitor cells (HSPCs) would benefit many HSPC transplantation and gene therapy/editing applications. However, current expansion technologies have been limited by a loss of multipotency and self-renewal properties ex vivo. We hypothesized that an ex vivo vascular niche would provide prohematopoietic signals to expand HSPCs while maintaining multipotency and self-renewal. To test this hypothesis, BM autologous CD34(+) cells were expanded in endothelial cell (EC) coculture and transplanted in nonhuman primates...
March 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28294393/the-new-msc-mscs-as-pericytes-are-sentinels-and-gatekeepers
#7
REVIEW
Arnold I Caplan
Human Mesenchymal Stem Cells, hMSCs, were first named over 25 years ago with the "stem cell" nomenclature derived from the fact that we and others could cause these cells to differentiate into a number of different mesodermal phenotypes in cell culture. The capacity to form skeletal tissue in vitro encouraged the use of hMSCs for the fabrication of tissue engineered skeletal repair tissue with subsequent transplantation to in vivo sites. With the current realization that MSCs are derived from perivascular cells, pericytes, and the immunomodulatory and trophic capabilities of MSCs in both in vitro and in vivo test systems, a complete re-evaluation of the role and functions of MSCs in the body was required...
March 15, 2017: Journal of Orthopaedic Research: Official Publication of the Orthopaedic Research Society
https://www.readbyqxmd.com/read/28292847/human-umbilical-cord-blood-borne-fibroblasts-contain-marrow-niche-precursors-that-form-a-bone-marrow-organoid-in-vivo
#8
Alice Pievani, Benedetto Sacchetti, Alessandro Corsi, Benedetta Rambaldi, Samantha Donsante, Valeria Scagliotti, Patrizia Vergani, Cristina Remoli, Andrea Biondi, Pamela G Robey, Mara Riminucci, Marta Serafini
Human umbilical cord blood (CB) has attracted much attention as a reservoir for functional hematopoietic stem and progenitor cells, and, recently, as a source of blood-borne fibroblasts (CB-BFs). Previously, we demonstrated that bone marrow stromal cell (BMSC) and CB-BF pellet cultures make cartilage in vitro Furthermore, upon in vivo transplantation, BMSC pellets remodelled into miniature bone/marrow organoids. Using this in vivo model, we asked whether CB-BF populations that express characteristics of the hematopoietic stem cell (HSC) niche contain precursors that reform the niche...
March 15, 2017: Development
https://www.readbyqxmd.com/read/28283030/impaired-osteogenesis-of-t1dm-bone-marrow-derived-stromal-cells-and-periosteum-derived-cells-and-their-differential-in-vitro-responses-to-growth-factor-rescue
#9
Tera M Filion, Jordan D Skelly, Henry Huang, Dale L Greiner, David C Ayers, Jie Song
BACKGROUND: Poor bone quality, increased fracture risks, and impaired bone healing are orthopedic comorbidities of type 1 diabetes (T1DM). Standard osteogenic growth factor treatments are inadequate in fully rescuing retarded healing of traumatic T1DM long bone injuries where both periosteal and bone marrow niches are disrupted. We test the hypotheses that osteogenesis of bone marrow-derived stromal cells (BMSCs) and periosteum-derived cells (PDCs), two critical skeletal progenitors in long bone healing, are both impaired in T1DM and that they respond differentially to osteogenic bone morphogenetic proteins (BMPs) and/or insulin-like growth factor-1 (IGF-1) rescue...
March 11, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28281084/the-role-and-clinical-implications-of-the-endosteal-niche-and-osteoblasts-in-regulating-leukemia
#10
REVIEW
S Azizidoost, V Vijay, C R Cogle, E Khodadi, N Saki
Osteoblasts are one among the critical components of the endosteal bone marrow (BM) niche. In addition to hematopoietic stem cell fate, their role in leukemogenesis as well as metastasis of a variety of cancers has been demonstrated in various studies. In this regard, endosteal niche can have a dual role as an initiator and protective role against leukemia. Knowledge of growth factors, chemokines and cytokines secreted by osteoblasts as well as their interaction with signaling pathways inform our understanding of the development, prognosis, recurrence and treatment of malignant BM diseases...
March 9, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28279922/biomaterial-enabled-delivery-of-sdf-1%C3%AE-at-the-ventral-side-of-breast-cancer-cells-reveals-a-crosstalk-between-cell-receptors-to-promote-the-invasive-phenotype
#11
Xi Qiu Liu, Laure Fourel, Fabien Dalonneau, Rabia Sadir, Salome Leal, Hugues Lortat-Jacob, Marianne Weidenhaupt, Corinne Albiges-Rizo, Catherine Picart
The SDF-1α chemokine (CXCL12) is a potent bioactive chemoattractant known to be involved in hematopoietic stem cell homing and cancer progression. The associated SDF-1α/CXCR4 receptor signaling is a hallmark of aggressive tumors, which can metastasize to distant sites such as lymph nodes, lung and bone. Here, we engineered a biomimetic tumoral niche made of a thin and soft polyelectrolyte film that can retain SDF-1α to present it, in a spatially-controlled manner, at the ventral side of the breast cancer cells...
February 27, 2017: Biomaterials
https://www.readbyqxmd.com/read/28279220/short-course-rapamycin-treatment-enables-engraftment-of-immunogenic-gene-engineered-bone-marrow-under-low-dose-irradiation-to-permit-long-term-immunological-tolerance
#12
Kunal H Bhatt, Rajeev Rudraraju, Jeremy F Brooks, Ji-Won Jung, Ryan Galea, James W Wells, Raymond J Steptoe
BACKGROUND: Application of genetically modified hematopoietic stem cells is increasingly mooted as a clinically relevant approach to protein replacement therapy, immune tolerance induction or conditions where both outcomes may be helpful. Hematopoietic stem and progenitor cell (HSPC)-mediated gene therapy often requires highly toxic pretransfer recipient conditioning to provide a 'niche' so that transferred HSPCs can engraft effectively and to prevent immune rejection of neoantigen-expressing engineered HSPCs...
March 9, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28265373/a-generalized-quantitative-antibody-homeostasis-model-regulation-of-b-cell-development-by-bcr-saturation-and-novel-insights-into-bone-marrow-function
#13
József Prechl
In a pair of articles, we present a generalized quantitative model for the homeostatic function of clonal humoral immune system. In this first paper, we describe the cycles of B-cell expansion and differentiation driven by B-cell receptor engagement. The fate of a B cell is determined by the signals it receives via its antigen receptor at any point of its lifetime. We express BCR engagement as a function of apparent affinity and free antigen concentration, using the range of 10(-14)-10(-3) M for both factors...
February 2017: Clinical & Translational Immunology
https://www.readbyqxmd.com/read/28264701/zoledronic-acid-alters-hematopoiesis-and-generates-breast-tumor-suppressive-bone-marrow-cells
#14
Jessalyn M Ubellacker, Marie-Therese Haider, Molly J DeCristo, Gloria Allocca, Nicola J Brown, Daniel P Silver, Ingunn Holen, Sandra S McAllister
BACKGROUND: The bone-targeting agent zoledronic acid (ZOL) increases breast cancer survival in subsets of patients, but the underlying reasons for this protective effect are unknown. ZOL modulates the activity of osteoclasts and osteoblasts, which form hematopoietic stem cell niches, and therefore may affect hematopoietic cells that play a role in breast cancer progression. METHOD: Immunocompetent and immunocompromised strains of mice commonly used for breast cancer research were injected with a single, clinically relevant dose of ZOL (100 μg/kg) or vehicle control...
March 6, 2017: Breast Cancer Research: BCR
https://www.readbyqxmd.com/read/28254840/extracellular-matrix-and-the-myeloid-in-myeloma-compartment-balancing-tolerogenic-and-immunogenic-inflammation-in-the-myeloma-niche
#15
REVIEW
Fotis Asimakopoulos, Chelsea Hope, Michael G Johnson, Adam Pagenkopf, Kimberly Gromek, Bradley Nagel
The last 10-15 years have witnessed a revolution in treating multiple myeloma, an incurable cancer of Ab-producing plasma cells. Advances in myeloma therapy were ushered in by novel agents that remodel the myeloma immune microenvironment. The first generation of novel agents included immunomodulatory drugs (thalidomide analogs) and proteasome inhibitors that target crucial pathways that regulate immunity and inflammation, such as NF-κB. This paradigm continued with the recent regulatory approval of mAbs (elotuzumab, daratumumab) that impact both tumor cells and associated immune cells...
March 2, 2017: Journal of Leukocyte Biology
https://www.readbyqxmd.com/read/28254837/osteopontin-attenuates-aging-associated-phenotypes-of-hematopoietic-stem-cells
#16
Novella Guidi, Mehmet Sacma, Ludger Ständker, Karin Soller, Gina Marka, Karina Eiwen, Johannes M Weiss, Frank Kirchhoff, Tanja Weil, Jose A Cancelas, Maria Carolina Florian, Hartmut Geiger
Upon aging, hematopoietic stem cells (HSCs) undergo changes in function and structure, including skewing to myeloid lineages, lower reconstitution potential and loss of protein polarity. While stem cell intrinsic mechanisms are known to contribute to HSC aging, little is known on whether age-related changes in the bone marrow niche regulate HSC aging. Upon aging, the expression of osteopontin (OPN) in the murine bone marrow stroma is reduced. Exposure of young HSCs to an OPN knockout niche results in a decrease in engraftment, an increase in long-term HSC frequency and loss of stem cell polarity...
March 2, 2017: EMBO Journal
https://www.readbyqxmd.com/read/28252222/irradiation-of-mesenchymal-stromal-cells-with-low-and-high-doses-of-alpha-particles-induces-senescence-and-or-apoptosis
#17
Nicola Alessio, Giuseppe Esposito, Giovanni Galano, Roberto De Rosa, Pasquale Anello, Gianfranco Peluso, Maria Antonella Tabocchini, Umberto Galderisi
The use of high-linear energy transfer charged particles is gaining attention as a medical tool because of the emission of radiations with an efficient cell-killing ability. Considerable interest has developed in the use of targeted alpha-particle therapy for the treatment of micrometastases. Moreover, the use of helium beams is gaining momentum, especially for treating pediatric tumors. We analyzed the effects of alpha particles on bone marrow mesenchymal stromal cells (MSCs), which have a subpopulation of stem cells capable of generating adipocytes, chondrocytes, and osteocytes...
March 2, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28250160/glucose-dependent-insulinotropic-polypeptide-receptor-deficiency-leads-to-impaired-bone-marrow-hematopoiesis
#18
Fernanda Dana Mantelmacher, Sigal Fishman, Keren Cohen, Metsada Pasmanik Chor, Yuichiro Yamada, Isabel Zvibel, Chen Varol
The bone marrow (BM) contains controlled specialized microenvironments, or niches, that regulate the quiescence, proliferation, and differentiation of hematopoietic stem and progenitor cells (HSPC). The glucose-dependent insulinotropic polypeptide (GIP) is a gut-derived incretin hormone that mediates postprandial insulin secretion and has anabolic effects on adipose tissue. Previous studies demonstrated altered bone microarchitecture in mice deficient for GIP receptor (Gipr(-/-) ), as well as the expression of high-affinity GIP receptor by distinct cells constructing the BM HSPC niche...
March 1, 2017: Journal of Immunology: Official Journal of the American Association of Immunologists
https://www.readbyqxmd.com/read/28247929/steady-state-peripheral-blood-provides-cells-with-functional-and-metabolic-characteristics-of-real-hematopoietic-stem-cells
#19
A Bourdieu, M Avalon, V Lapostolle, S Ismail, M Mombled, C Debeissat, M Guérinet, P Duchez, J Chevaleyre, M Vlaski-Lafarge, A Villacreces, V Praloran, Z Ivanovic, P Brunet de la Grange
Hematopoietic stem cells (HSCs), which are located in the bone marrow, also circulate in cord and peripheral blood. Despite high availability, HSCs from steady state peripheral blood (SSPB) are little known and not used for research or cell therapy. We thus aimed to characterize and select HSCs from SSPB by a direct approach with a view to delineating their main functional and metabolic properties and the mechanisms responsible for their maintenance. We chose to work on Side Population (SP) cells which are highly enriched in HSCs in mouse, human bone marrow, and cord blood...
March 1, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28247013/latest-perspectives-on-macrophages-in-bone-homeostasis
#20
REVIEW
Aline Bozec, Didier Soulat
Knowledge about macrophages residing in the bone, also known as osteal macrophages or osteomacs, is still limited. A hallmark of this peculiar myeloid population is the expression of macrophage markers distinct from the markers found on osteoclast surface. In bone, osteomacs are in contact with osteoblasts, where they are involved in regulating bone homeostasis. However, additional macrophage subtypes already present in the bone marrow or recruited from the blood circulation could have further functions, which could be all important for the maintenance of the bone architecture and its associated functions...
February 28, 2017: Pflügers Archiv: European Journal of Physiology
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