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Bone niche

Sho Kurihara, Masato Fujioka, Tomohiko Yoshida, Makoto Koizumi, Kaoru Ogawa, Hiromi Kojima, Hirotaka James Okano
Hearing research has long been facilitated by rodent models, although in some diseases, human symptoms cannot be recapitulated. The common marmoset (Callithrix jacchus) is a small, easy-to-handle New World monkey which has a similar anatomy of the temporal bone, including the middle ear ossicular chains and inner ear to humans, than in comparison with that of rodents. Here, we report a reproducible, safe, and rational surgical approach to the cochlear round window niche for the drug delivery to the inner ear of the common marmoset...
February 27, 2018: Journal of Visualized Experiments: JoVE
Joshua T Eggold, Erinn B Rankin
The regulation of erythropoiesis in the bone marrow microenvironment is a carefully orchestrated process that is dependent upon both systemic and local cues. Systemic erythropoietin (EPO) production by renal interstitial cells plays a critical role in maintaining erythropoietic homeostasis. In addition, there is increasing clinical and preclinical data linking changes in EPO and erythropoiesis to altered skeletal homeostasis, suggesting a functional relationship between the regulation of erythropoiesis and bone homeostasis...
March 15, 2018: Bone
Kyohei Nakamura, Sahar Kassem, Alice Cleynen, Marie-Lorraine Chrétien, Camille Guillerey, Eva Maria Putz, Tobias Bald, Irmgard Förster, Slavica Vuckovic, Geoffrey R Hill, Seth L Masters, Marta Chesi, P Leif Bergsagel, Hervé Avet-Loiseau, Ludovic Martinet, Mark J Smyth
Tumor-promoting inflammation and avoiding immune destruction are hallmarks of cancer. Here, we demonstrate that the pro-inflammatory cytokine interleukin (IL)-18 is critically involved in these hallmarks in multiple myeloma (MM). Mice deficient for IL-18 were remarkably protected from Vk∗ MYC MM progression in a CD8+ T cell-dependent manner. The MM-niche-derived IL-18 drove generation of myeloid-derived suppressor cells (MDSCs), leading to accelerated disease progression. A global transcriptome analysis of the immune microenvironment in 73 MM patients strongly supported the negative impact of IL-18-driven MDSCs on T cell responses...
March 1, 2018: Cancer Cell
Karin Kohlstedt, Caroline Trouvain, Timo Frömel, Thomas Mudersbach, Reinhard Henschler, Ingrid Fleming
In addition to being a peptidase, the angiotensin-converting enzyme (ACE) can be phosphorylated and involved in signal transduction. We evaluated the role of ACE in granulocyte-colony-stimulating factor (G-CSF)-induced hematopoietic progenitor cell (HPC) mobilization and detected a significant increase in mice-lacking ACE. Transplantation experiments revealed that the loss of ACE in the HPC microenvironment rather than in the HPCs increased mobilization. Indeed, although ACE was expressed by a small population of bone-marrow cells, it was more strongly expressed by endosteal bone...
March 17, 2018: Basic Research in Cardiology
Emma V Morris, Claire M Edwards
Multiple Myeloma (MM) is an incurable haematological malignancy and is the second most common blood cancer in adults; it is caused by the clonal expansion of abnormal plasma cells within the bone marrow characterized by osteolytic bone lesions, bone pain, renal disease, and immunodeficiency. MM cells infiltrate the bone marrow where they hijack the microenvironment to sustain growth and survival. The contribution to this process by resident bone cells is well defined. However, the role of bone marrow adipocytes is less clear...
March 13, 2018: Bone
Thais Assis-Ribas, Maria Fernanda Forni, Sheila Maria Brochado Winnischofer, Mari Cleide Sogayar, Marina Trombetta-Lima
Mesenchymal stem cells (MSCs) are stromal cells that display self-renewal and multipotent differentiation capacity. The repertoire of mature cells generated ranges but is not restricted to: fat, bone and cartilage. Their potential importance for both cell therapy and maintenance of in vivo homeostasis is indisputable. Nonetheless, both their in vivo identity and use in cell therapy remain elusive. A drawback generated by this fact is that little is known about the MSC niche and how it impacts differentiation and homeostasis maintenance...
March 12, 2018: Developmental Biology
Michelle Brault, Tayla M Olsen, Jennifer Martinez, Daniel B Stetson, Andrew Oberst
The sensing of viral nucleic acids within the cytosol is essential for the induction of innate immune responses following infection. However, this sensing occurs within cells that have already been infected. The death of infected cells can be beneficial to the host by eliminating the virus's replicative niche and facilitating the release of inflammatory mediators. In this study, we show that sensing of intracellular DNA or RNA by cGAS-STING or RIG-I-MAVS, respectively, leads to activation of RIPK3 and necroptosis in bone marrow-derived macrophages...
March 14, 2018: Journal of Immunology: Official Journal of the American Association of Immunologists
Atsuko Kayaba, Ari Itoh-Nakadai, Kunimichi Niibe, Matsuyuki Shirota, Ryo Funayama, Akiko Sugahara-Tobinai, Yi Li Wong, Masanori Inui, Keiko Nakayama, Toshiyuki Takai
Plasma cells (PCs) acquiring with long lives in bone marrow (BM) play a pivotal role in the humoral arm of immunological memory. The PCs reside in a special BM niche and produce antibodies against past-encountered pathogens or vaccine components for a long time. In BM, cysteine-X-cysteine (CXC) chemokine receptor type 4-expressing PCs and myeloid cells such as dendritic cells are attracted to and held by CXC chemokine ligand 12-secreting stromal cells, where survival of the PCs is supported by soluble factors such as IL-6 and a proliferation-inducing ligand or APRIL produced by neighboring myeloid cells...
February 24, 2018: International Immunology
Maile K Hollinger, Valentina Giudice, Nicole A Cummings, Guillermo Rivell, Hansheng Zhang, Sachiko Kajigaya, Keyvan Keyvanfar, Jichun Chen, Xingmin Feng, Neal S Young
While PD-1 blockade has revolutionized cancer immunotherapy, immune-related adverse events (irAEs) present life-threatening complications. Recent reports of aplastic anemia (AA) as irAEs implicate PD-1/PD-L1 as important in preventing immune-mediated destruction of the hematopoietic niche. Infusion of PD-1-deficient (PD-1 KO) lymph node (LN) cells into minor-antigen mismatched mice resulted in early mortality, as well as more severe BM hypoplasia, anemia, and BM microarchitecture disruption in PD-1 KO LN-infused mice relative to mice that received B6 LN cell infusion...
March 7, 2018: Experimental Hematology
Pingnan Xiao, Monika Dolinska, Lakshmi Sandhow, Makoto Kondo, Anne-Sofie Johansson, Thibault Bouderlique, Ying Zhao, Xidan Li, Marios Dimitriou, George Z Rassidakis, Eva Hellström-Lindberg, Nagahiro Minato, Julian Walfridsson, David T Scadden, Mikael Sigvardsson, Hong Qian
Mutations of signal-induced proliferation-associated gene 1 ( SIPA1 ), a RAP1 GTPase-activating protein, were reported in patients with juvenile myelomonocytic leukemia, a childhood myelodysplastic/myeloproliferative neoplasm (MDS/MPN). Sipa1 deficiency in mice leads to the development of age-dependent MPN. However, Sipa1 expression in bone marrow (BM) microenvironment and its effect on the pathogenesis of MPN remain unclear. We here report that Sipa1 is expressed in human and mouse BM stromal cells and downregulated in these cells from patients with MPN or MDS/MPN at diagnosis...
March 13, 2018: Blood Advances
Bin Zhang, Le Xuan Truong Nguyen, Ling Li, Dandan Zhao, Bijender Kumar, Herman Wu, Allen Lin, Francesca Pellicano, Lisa Hopcroft, Yu-Lin Su, Mhairi Copland, Tessa L Holyoake, Calvin J Kuo, Ravi Bhatia, David S Snyder, Haris Ali, Anthony S Stein, Casey Brewer, Huafeng Wang, Tinisha McDonald, Piotr Swiderski, Estelle Troadec, Ching-Cheng Chen, Adrienne Dorrance, Vinod Pullarkat, Yate-Ching Yuan, Danilo Perrotti, Nadia Carlesso, Stephen J Forman, Marcin Kortylewski, Ya-Huei Kuo, Guido Marcucci
Leukemia stem cells (LSCs) in individuals with chronic myelogenous leukemia (CML) (hereafter referred to as CML LSCs) are responsible for initiating and maintaining clonal hematopoiesis. These cells persist in the bone marrow (BM) despite effective inhibition of BCR-ABL kinase activity by tyrosine kinase inhibitors (TKIs). Here we show that although the microRNA (miRNA) miR-126 supported the quiescence, self-renewal and engraftment capacity of CML LSCs, miR-126 levels were lower in CML LSCs than in long-term hematopoietic stem cells (LT-HSCs) from healthy individuals...
March 5, 2018: Nature Medicine
Ken Morita, Chieko Tokushige, Shintaro Maeda, Hiroki Kiyose, Mina Noura, Atsushi Iwai, Maya Yamada, Gengo Kashiwazaki, Junichi Taniguchi, Toshikazu Bando, Masahiro Hirata, Tatsuki R Kataoka, Tatsutoshi Nakahata, Souichi Adachi, Hiroshi Sugiyama, Yasuhiko Kamikubo
Although the function of Runt-related (RUNX) transcription factors has been well characterized in leukemogenesis and regarded as an ideal target in antileukemia strategies, the effect of RUNX-inhibition therapy on bone marrow niche cells andr its impact on the engraftment of acute myeloid leukemia (AML) cells have largely been unknown. Here, we provide evidence suggesting the possible involvement of RUNX transcription factors in the transactivation of E-selectin , a member of selectin family of cell adhesion molecules, on the vascular endothelial cells of the mice bone marrow niche...
March 13, 2018: Blood Advances
Subhadip Hajra, Arup Ranjan Patra, Abhishek Basu, Sudin Bhattacharya
Doxorubicin (DOX) is an anthracycline group of antibiotic available for the treatment of broad spectrum of human cancers. However, patient receiving DOX-therapy, myelosuppression and genotoxicity which may lead to secondary malignancy and dose dependent cardiotoxicity is an imperative adverse effect. Mechanisms behind the DOX-induced toxicities are increased level of oxidative damage, inflammation and apoptosis. Therefore, in search of a potential chemoprotectant, naturally occurring glucosinolate breakdown product Indole-3-Carbinol (I3C) was evaluated against DOX-induced toxicities in Swiss albino mice...
February 26, 2018: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Bo Gao, Xisheng Lin, Huan Jing, Jing Fan, Chenchen Ji, Qiang Jie, Chao Zheng, Di Wang, Xiaolong Xu, Yaqian Hu, Weiguang Lu, Zhuojing Luo, Liu Yang
Aging drives the accumulation of senescent cells (SnCs) including stem/progenitor cells in bone marrow, which contributes to aging-related bone degenerative pathologies. Local elimination of SnCs has been shown as potential treatment for degenerative diseases. As LepR+ mesenchymal stem/progenitor cells (MSPCs) in bone marrow are the major population for forming bone/cartilage and maintaining HSCs niche, whether local elimination of senescent LepR+ MSPCs delays aging-related pathologies and improves local microenvironment need to be well defined...
February 28, 2018: Aging Cell
Anjum B Khan, Ben Carpenter, Pedro Santos E Sousa, Constandina Pospori, Reema Khorshed, James Griffin, Pedro Veliça, Mathias Zech, Sara Ghorashian, Calum Forrest, Sharyn Thomas, Sara Gonzalez Anton, Maryam Ahmadi, Angelika Holler, Barry Flutter, Zaida Ramirez-Ortiz, Terry K Means, Clare L Bennett, Hans Stauss, Emma Morris, Cristina Lo Celso, Ronjon Chakraverty
A key predictor for the success of gene-modified T cell therapies for cancer is the persistence of transferred cells in the patient. The propensity of less differentiated memory T cells to expand and survive efficiently has therefore made them attractive candidates for clinical application. We hypothesized that re-directing T cells to specialized niches in the bone marrow (BM) that support memory differentiation would confer increased therapeutic efficacy. We show that overexpression of chemokine receptor CXCR4 in CD8+ T cells (TCXCR4) enhanced their migration towards vascular-associated CXCL12+ cells in the BM and increased their local engraftment...
February 27, 2018: Journal of Clinical Investigation
O Kos, C Alexander, K Brandenburg, Z Chen, A Heini, D Heumann, I Khatri, J P Mach, E T Rietschel, A Tersikh, A J Ulmer, T Waelli, K Yu, U Zähringer, R M Gorczynski
We have shown that an altered tissue redox environment in mice lacking either murine beta Hemoglobin major (Hgbβma KO) or minor (Hgbβmi KO) regulates inflammation. The REDOX environment in marrow stem cell niches also control differentiation pathways. We investigated osteoclastogenesis (OC)/osteoblastogenesis (OB), in bone cultures derived from untreated or FSLE-treated WT, Hgbβma KO or Hgbβmi KO mice. Marrow mesenchymal cells from 10d pre-cultures were incubated on an osteogenic matrix for 21d prior to analysis of inflammatory cytokine release into culture supernatants, and relative OC:OB using (TRAP:BSP, RANKL:OPG) mRNA expression ratios and TRAP or Von Kossa staining...
February 22, 2018: International Immunopharmacology
Florence Zylbersztejn, Mario Flores-Violante, Thibault Voeltzel, Franck-Emmanuel Nicolini, Sylvain Lefort, Véronique Maguer-Satta
The microenvironment (niche) governs the fate of stem cells (SC) by balancing self-renewal and differentiation. Increasing evidence indicates that the tumor niche plays an active role in cancer but its (important) properties for tumor initiation progression and resistance remain to be identified. Clinical data show that leukemic stem cells (LSC) survival is responsible for disease persistence and drug resistance probably due to their sustained interactions with the tumor niche. The Bone Morphogenetic Protein (BMP) signaling is a key pathway controlling stem cells and their niche, such as BMP2 and BMP4 important in both normal and cancer context...
February 22, 2018: Experimental Hematology
Yookyung Jung, Joel A Spencer, Anthony P Raphael, Juwell W Wu, Clemens Alt, Judith R Runnels, Briaira Geiger, Charles P Lin
The bone marrow is a unique microenvironment where blood cells are produced and released into the circulation. At the top of the blood cell lineage are the hematopoietic stem cells (HSC), which are thought to reside in close association with the bone marrow vascular endothelial cells (Morrison and Scadden, Nature 505:327-334, 2014). Recent efforts at characterizing the HSC niche have prompted us to make close examinations of two distinct types of blood vessel in the bone marrow, the arteriolar vessels originating from arteries and sinusoidal vessels connected to veins...
2018: Methods in Molecular Biology
Rahul Kumar, P Sonika Godavarthy, Daniela S Krause
The bone marrow microenvironment (BMM) is the 'domicile' of hematopoietic stem cells, as well as of malignant processes that can develop there. Multiple and complex interactions with the BMM influence hematopoietic stem cell (HSC) physiology, but also the pathophysiology of hematological malignancies. Reciprocally, hematological malignancies alter the BMM, in order to render it more hospitable for malignant progression. In this Cell Science at a Glance article and accompanying poster, we highlight concepts of the normal and malignant hematopoietic stem cell niches...
February 22, 2018: Journal of Cell Science
Stephen T Reece, Alexis Vogelzang, Julia Tornack, Wolfgang Bauer, Ulrike Zedler, Sandra Schommer-Leitner, Georg Stingl, Fritz Melchers, Stefan H E Kaufmann
Persistence of Mycobacterium tuberculosis within human bone marrow stem cells has been identified as a potential bacterial niche during latent tuberculosis. Using a murine model of tuberculosis, we show here that bone marrow stem and progenitor cells containing M. tuberculosis propagated tuberculosis when transferred to naive mice, given that both transferred cells and recipient mice were unable to express inducible nitric oxide synthase, which mediates killing of intracellular bacteria via nitric oxide. Our findings suggest that bone marrow stem and progenitor cells containing M...
February 17, 2018: Journal of Infectious Diseases
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