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https://www.readbyqxmd.com/read/28534115/complexity-of-bone-marrow-hematopoietic-stem-cell-niche
#1
REVIEW
Noboru Asada, Shoichiro Takeishi, Paul S Frenette
Hematopoietic stem cells (HSCs) that produce a variety of hematopoietic lineage cells throughout the life reside in specialized microenvironment called "niche" in the bone marrow (BM) where they are tightly regulated. With the recent advances in experimental technologies enabling the selective deletion of molecules, various types of cells in the BM have been proposed to contribute to HSC niche activity. Among these are stromal cells closely associated with the vasculature. In this review, we provide an overview of recent advances in HSC niche research, and focus on the studies describing the functional roles of perivascular cells for HSC maintenance and mobilization...
May 22, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28528702/detailed-characterization-of-mesenchymal-stem-stromal-cells-from-a-large-cohort-of-aml-patients-demonstrates-a-definitive-link-to-treatment-outcomes
#2
Rafael Diaz de la Guardia, Belen Lopez-Millan, Jessie R Lavoie, Clara Bueno, Julio Castaño, Maite Gómez-Casares, Susana Vives, Laura Palomo, Manel Juan, Julio Delgado, Maria L Blanco, Josep Nomdedeu, Alberto Chaparro, Jose Luis Fuster, Eduardo Anguita, Michael Rosu-Myles, Pablo Menéndez
Bone marrow mesenchymal stem/stromal cells (BM-MSCs) are key components of the hematopoietic niche thought to have a direct role in leukemia pathogenesis. BM-MSCs from patients with acute myeloid leukemia (AML) have been poorly characterized due to disease heterogeneity. We report a functional, genetic, and immunological characterization of BM-MSC cultures from 46 AML patients, stratified by molecular/cytogenetics into low-risk (LR), intermediate-risk (IR), and high-risk (HR) subgroups. Stable MSC cultures were successfully established and characterized from 40 of 46 AML patients irrespective of the risk subgroup...
May 18, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28524857/a-defined-metabolic-state-in-pre-b-cells-governs-b-cell-development-and-is-counterbalanced-by-swiprosin-2-efhd1
#3
Merle Stein, Sebastian Dütting, Dimitrios Mougiakakos, Michael Bösl, Kristin Fritsch, Dorothea Reimer, Sophia Urbanczyk, Tobit Steinmetz, Wolfgang Schuh, Aline Bozec, Thomas H Winkler, Hans-Martin Jäck, Dirk Mielenz
B-cell development in the bone marrow comprises proliferative and resting phases in different niches. We asked whether B-cell metabolism relates to these changes. Compared to pro B and small pre B cells, large pre B cells revealed the highest glucose uptake and ROS but not mitochondrial mass, whereas small pre B cells exhibited the lowest mitochondrial membrane potential. Small pre B cells from Rag1(-/-);33.C9 μ heavy chain knock-in mice revealed decreased glycolysis (ECAR) and mitochondrial spare capacity compared to pro B cells from Rag1(-/-) mice...
May 19, 2017: Cell Death and Differentiation
https://www.readbyqxmd.com/read/28516389/microenvironmental-scenario-of-the-bone-marrow-of-inorganic-arsenic-exposed-experimental-mice
#4
Jacintha Archana Pereira, Sujata Law
Exposure to arsenic on a regular basis, mainly through drinking water, agricultural pesticide, and sometimes therapeutic dose, results in various diseases of different tissues including the bone marrow hematopoietic system. Hematopoiesis is a dynamic process by which bone marrow (BM) hematopoietic stem/progenitor cells (HSPCs) generate a relatively constant pool of functionally mature blood cells by the support of microenvironmental components. The present study has been aimed to understand stem cell microenvironmental status during arsenic toxicity and the consequent reflection of dysregulation involving the hematopoietic machinery in experimental mice...
May 17, 2017: Biological Trace Element Research
https://www.readbyqxmd.com/read/28513874/%C3%AE-3-adrenergic-regulation-of-epc-features-through-manipulation-of-the-bone-marrow-msc-niche
#5
Rana Vafaei, Seyed Mahdi Nassiri, Vahid Siavashi
Mesenchymal stem cells (MSCs) reside in a specific niche in the bone marrow however biological features of this niche are still not fully understood. Given the interactions of MSCs with endothelial cells in different tissues, bone marrow MSC niche may influence the biological features of endothelial progenitor cells (EPCs). To understand the role of the sympathetic nervous system in regulation of the MSC niche, we examined whether the manipulation of the MSC niche via β3-adrenergic signals will affect EPC features...
May 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28513838/the-emerging-role-of-npnt-in-tissue-injury-repair-and-bone-homeostasis
#6
REVIEW
Youqiang Sun, Vincent Kuek, Heng Qiu, Jennifer Tickner, Leilei Chen, Haibin Wang, Wei He, Jiake Xu
Nephronectin (NPNT), a highly conserved extracellular matrix protein, plays an important role in regulating cell adhesion, differentiation, spreading and survival. NPNT protein belongs to epidermal growth factor (EGF)-like superfamily and exhibits several common structural determinants; including EGF-like repeat domains, MAM domain (Meprin, A5 Protein, and Receptor Protein-Tyrosine Phosphatase µ), RGD motif (Arg-Gly-Asp) and a coiled-coil domain. It regulates integrins-mediated signaling pathways via the interaction of its RGD motif with integrin α8β1...
May 17, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28513105/hair-follicle-specific-acvr1-alk2-critically-affects-skin-morphogenesis-and-attenuates-wound-healing
#7
Michael Sorkin, Shailesh Agarwal, Kavitha Ranganathan, Shawn Loder, David Cholok, David Fireman, John Li, Shuli Li, Bin Zhao, Yuji Mishina, Paul Cederna, Benjamin Levi
The bone morphogenic protein signaling (BMP) is intricately involved in the quiescence and regulation of stem cells through activation of BMP receptors. Hair follicle stem cells play a critical role in cutaneous homeostasis and regeneration. Here, we utilize a novel mouse model with targeted overexpression of the BMP receptor ALK2/ACVR1 in hair follicle stem cells, to characterize its role in skin development and postnatal wound healing. Initial histologic evaluation demonstrated significant dysregulation in hair follicle morphogenesis in mutant mice...
May 17, 2017: Wound Repair and Regeneration
https://www.readbyqxmd.com/read/28512561/bone-marrow-homing-and-engraftment-defects-of-human-hematopoietic-stem-and-progenitor-cells
#8
REVIEW
Giovanni Caocci, Marianna Greco, Giorgio La Nasa
Homing of hematopoietic stem cells (HSC) to their microenvironment niches in the bone marrow is a complex process with a critical role in repopulation of the bone marrow after transplantation. This active process allows for migration of HSC from peripheral blood and their successful anchoring in bone marrow before proliferation. The process of engraftment starts with the onset of proliferation and must, therefore, be functionally dissociated from the former process. In this overview, we analyze the characteristics of stem cells (SCs) with particular emphasis on their plasticity and ability to find their way home to the bone marrow...
2017: Mediterranean Journal of Hematology and Infectious Diseases
https://www.readbyqxmd.com/read/28509582/tariquidar-sensitizes-multiple-myeloma-cells-to-proteasome-inhibitors-via-reduction-of-hypoxia-induced-p-gp-mediated-drug-resistance
#9
Barbara Muz, Hubert D Kusdono, Feda Azab, Pilar de la Puente, Cinzia Federico, Mark Fiala, Ravi Vij, Noha N Salama, Abdel Kareem Azab
Multiple myeloma (MM) presents a poor prognosis and high lethality of patients due to development of drug resistance. P-glycoprotein (P-gp), a drug-efflux transporter, is upregulated in MM patients post-chemotherapy and is involved in the development of drug resistance since many anti-myeloma drugs (including proteasome inhibitors) are P-gp substrates. Hypoxia develops in the bone marrow niche during MM progression and has long been linked to chemoresistance. Additionally, hypoxia-inducible transcription factor (HIF-1α) was demonstrated to directly regulate P-gp expression...
May 16, 2017: Leukemia & Lymphoma
https://www.readbyqxmd.com/read/28501940/common-extracellular-matrix-regulation-of-myeloid-cell-activity-in-the-bone-marrow-and-tumor-microenvironments
#10
REVIEW
Sabina Sangaletti, Claudia Chiodoni, Claudio Tripodo, Mario P Colombo
The complex interaction between cells undergoing transformation and the various stromal and immunological cell components of the tumor microenvironment (TME) crucially influences cancer progression and diversification, as well as endowing clinical and prognostic significance. The immunosuppression characterizing the TME depends on the recruitment and activation of different cell types including regulatory T cells, myeloid-derived suppressor cells, and tumor-associated macrophages. Less considered is the non-cellular component of the TME...
May 13, 2017: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/28499894/pathophysiology-of-bone-metastases-from-solid-malignancies
#11
Philippe Clézardin
Bone metastases are common complications of many cancers. Among the mechanisms that set the scene for the development of bone metastases, several are shared by all forms of metastatic dissemination (pre-metastatic niche formation and chemotactic attraction of malignant cells, which invade the host tissue) and others are specific of bone tissue (homing of malignant cells to bone marrow niches and acquisition of an osteomimetic cell phenotype). After a latency period that can last several years, the malignant cells can proliferate into tumors that alter the normal bone remodeling process by inducing dysregulation of osteoblast and osteoclast function...
May 9, 2017: Joint, Bone, Spine: Revue du Rhumatisme
https://www.readbyqxmd.com/read/28495640/sources-of-hematopoietic-stem-and-progenitor-cells-and-methods-to-optimize-yields-for-clinical-cell-therapy
#12
REVIEW
Sandhya R Panch, James Szymanski, Bipin N Savani, David F Stroncek
Bone marrow (BM) aspirates, mobilized peripheral blood (PB) and umbilical cord blood (UCB) have developed as graft sources of hematopoietic stem and progenitor cells (HSPC) for stem cell transplantation and other cellular therapeutics. Individualized techniques are necessary to enhance graft HSPC yields and cell quality from each graft source. BM aspirates yield adequate CD34+cells but can result in relative delays in engraftment. Granulocyte-colony stimulating factor (G-CSF) primed bone marrow HSPC may facilitate faster engraftment while minimizing graft-versus-host disease (GVHD) in certain patient subsets...
May 8, 2017: Biology of Blood and Marrow Transplantation
https://www.readbyqxmd.com/read/28494752/mda-met-conditioned-medium-augments-the-chemoattractant-dependent-migration-of-mda-met-cells-towards-hfob-conditioned-medium-and-increases-collagenase-activity
#13
Karis Chin-Quee, Henry J Donahue
BACKGROUND: Metastasis of breast cancer displays site-specificity towards bone. Recently, studies have emerged indicating that primary tumors may remotely influence creation of a pre-metastatic niche. In this study, we used human fetal osteoblastic cells and MDA-MET, a metastatic and preferentially bone homing derivative of the breast cancer cell line MDA-MB-231. We examined 1) whether secreted factors from MDA-MET cells increase generation of chemoattractants by human foetal osteoblastic cells 2) whether MDA-MET cells were responsive to these chemoattractants and 3) the identity of these chemoattractants...
May 11, 2017: BMC Cancer
https://www.readbyqxmd.com/read/28492285/prolonged-intracellular-accumulation-of-light-inducible-nanoparticles-in-leukemia-cells-allows-their-remote-activation
#14
Carlos Boto, Emanuel Quartin, Yijun Cai, Alberto Martín-Lorenzo, María Begoña García Cenador, Sandra Pinto, Rajeev Gupta, Tariq Enver, Isidro Sánchez-García, Dengli Hong, Ricardo Pires das Neves, Lino Ferreira
Leukaemia cells that are resistant to conventional therapies are thought to reside in protective niches. Here, we describe light-inducible polymeric retinoic acid (RA)-containing nanoparticles (NPs) with the capacity to accumulate in the cytoplasm of leukaemia cells for several days and release their RA payloads within a few minutes upon exposure to blue/UV light. Compared to NPs that are not activated by light exposure, these NPs more efficiently reduce the clonogenicity of bone marrow cancer cells from patients with acute myeloid leukaemia (AML) and induce the differentiation of RA-low sensitive leukaemia cells...
May 11, 2017: Nature Communications
https://www.readbyqxmd.com/read/28476191/analysis-of-normal-hematopoietic-stem-and-progenitor-cell-contents-in-childhood-acute-leukemia-bone-marrow
#15
Juan Carlos Balandrán, Eduardo Vadillo, David Dozal, Alfonso Reyes-López, Antonio Sandoval-Cabrera, Merle Denisse Laffont-Ortiz, Jessica L Prieto-Chávez, Armando Vilchis-Ordoñez, Henry Quintela-Nuñez Del Prado, Héctor Mayani, Juan Carlos Núñez-Enríquez, Juan Manuel Mejía-Aranguré, Briceida López-Martínez, Elva Jiménez-Hernández, Rosana Pelayo
BACKGROUND AND AIMS: Childhood acute leukemias (AL) are characterized by the excessive production of malignant precursor cells at the expense of effective blood cell development. The dominance of leukemic cells over normal progenitors may result in either direct suppression of functional hematopoiesis or remodeling of microenvironmental niches, contributing to BM failure and AL-associated mortality. We undertook this study to investigate the contents and functional activity of hematopoietic stem/progenitor cells (HSPC) and their relationship to immune cell production and risk status in AL pediatric patients...
November 2016: Archives of Medical Research
https://www.readbyqxmd.com/read/28471165/nanoscale-silk-hydroxyapatite-hydrogels-for-injectable-bone-biomaterials
#16
Zhaozhao Ding, Hongyan Han, Zhihai Fan, Haijun Lu, Yonghuan Sang, Yuling Yao, Qingqing Cheng, Qiang Lu, David L Kaplan
Injectable hydrogel systems are important bone substitutes for regeneration because of their handling properties and the ability to fill irregular defects. Silk-hydroxyapatite composite materials with silk nanofibers in hydrogels were prepared and used as biomaterials for osteogenesis. These thixotropic silk nanofiber hydrogels and water-dispersible silk-HA nanoparticles were blended to form injectable nanoscale systems with a homogeneous distribution of a high HA content [60% (w/w)] to imitate bone niche. A modulus of ∼21 kPa was also achieved following the addition of HA in the systems, providing physical cues to induce osteodifferentiation...
May 11, 2017: ACS Applied Materials & Interfaces
https://www.readbyqxmd.com/read/28464921/human-adult-mesangiogenic-progenitor-cells-reveal-an-early-angiogenic-potential-which-is-lost-after-mesengenic-differentiation
#17
Marina Montali, Francesca M Panvini, Serena Barachini, Francesca Ronca, Vittoria Carnicelli, Stefano Mazzoni, Iacopo Petrini, Simone Pacini
BACKGROUND: Mesangiogenic progenitor cells (MPCs) have shown the ability to differentiate in-vitro toward mesenchymal stromal cells (MSCs) as well as angiogenic potential. MPCs have so far been described in detail as progenitors of the mesodermal lineage and appear to be of great significance in tissue regeneration and in hemopoietic niche regulation. On the contrary, information regarding the MPC angiogenic process is still incomplete and requires further clarification. In particular, genuine MPC angiogenic potential should be confirmed in-vivo...
May 2, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28463768/homoharringtonine-enhances-bortezomib-antimyeloma-activity-in-myeloma-cells-adhesion-to-bone-marrow-stromal-cells-and-in-scid-mouse-xenografts
#18
Ping Chen, Qin Yuan, Hui Yang, Xiaofang Wen, Peidong You, Diyu Hou, Jieqiong Xie, Yu Cheng, Huifang Huang
Despite the great progress in the treatment, multiple myeloma (MM) still remains incurable. Bortezomib (BTZ), a reversible inhibitor of the 26S proteasome, is very effective against MM but unable to eradicate the MM cells in bone marrow niche eventually causing the disease relapse. Homoharringtonine (HHT) is a known anti-leukemia drug that inhibits MM both in vitro and in vivo. This study aimed to investigate whether HHT could potentiate the anti-tumor activity of BTZ in MM cells cocultured with bone marrow stromal cells and in vivo xenograft models...
April 25, 2017: Leukemia Research
https://www.readbyqxmd.com/read/28460416/the-skeletal-cell-derived-molecule-sclerostin-drives-bone-marrow-adipogenesis
#19
Heather Fairfield, Carolyne Falank, Elizabeth Harris, Victoria Demambro, Michelle McDonald, Jessica A Pettit, Sindhu T Mohanty, Peter Croucher, Ina Kramer, Michaela Kneissel, Clifford J Rosen, Michaela R Reagan
The bone marrow niche is a dynamic and complex microenvironment that can both regulate, and be regulated by the bone matrix. Within the bone marrow (BM), mesenchymal stromal cell (MSC) precursors reside in a multi-potent state and retain the capacity to differentiate down osteoblastic, adipogenic, or chondrogenic lineages in response to numerous biochemical cues. These signals can be altered in various pathological states including, but not limited to, osteoporotic-induced fracture, systemic adiposity, and the presence of bone-homing cancers...
April 29, 2017: Journal of Cellular Physiology
https://www.readbyqxmd.com/read/28459117/the-human-thymus-perivascular-space-is-a-functional-niche-for-viral-specific-plasma-cells
#20
Sarah Nuñez, Carolina Moore, Baoshan Gao, Kortney Rogers, Yessia Hidalgo, Pedro J Del Nido, Susan Restaino, Yoshifumi Naka, Govind Bhagat, Joren C Madsen, María Rosa Bono, Emmanuel Zorn
The human thymus is susceptible to viral infections that can severely alter thymopoiesis and compromise the mechanisms of acquired tolerance to self-antigens. In humans, plasma cells residing primarily in the bone marrow confer long-lasting protection to common viruses by secreting antigen-specific antibodies. Since the thymus also houses B cells, we examined the phenotypic complexity of these thymic resident cells and their possible protective role against viral infections. Using tissue specimens collected from subjects ranging in age from 5 days to 71 years, we found that starting during the first year of life, CD138(+) plasma cells (PC) begin accumulating in the thymic perivascular space (PVS) where they constitutively produce IgG without the need for additional stimulation...
December 2016: Science Immunology
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