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Bone marrow

Antonella Conforti, Nadia Starc, Simone Biagini, Luigi Tomao, Angela Pitisci, Mattia Algeri, Pietro Sirleto, Antonio Novelli, Giulia Grisendi, Olivia Candini, Cintia Carella, Massimo Dominici, Franco Locatelli, Maria Ester Bernardo
The risk of malignant transformation of ex-vivo expanded human mesenchymal stromal cells (huMSCs) has been debated in the last years; however, the biosafety of these cells after exposure to supramaximal physical and chemical stress has never been systematically investigated.We established an experimental in vitro model to induce supramaximal physical (ionizing radiation, IR) and chemical (starvation) stress on ex-vivo expanded bone marrow (BM)-derived huMSCs and investigated their propensity to undergo malignant transformation...
October 15, 2016: Oncotarget
Jana Jakubikova, Danka Cholujova, Teru Hideshima, Paulina Gronesova, Andrea Soltysova, Takeshi Harada, Jungnam Joo, Sun-Young Kong, Raphael E Szalat, Paul G Richardson, Nikhil C Munshi, David M Dorfman, Kenneth C Anderson
Specific niches within the tumor bone marrow (BM) microenvironment afford a sanctuary for multiple myeloma (MM) clones due to stromal cell-tumor cell interactions, which confer survival advantage and drug resistance. Defining the sequelae of tumor cell interactions within the MM niches on an individualized basis may provide the rationale for personalized therapies. To mimic the MM niche, we here describe a new 3D co-culture ex-vivo model in which primary MM patient BM cells are co-cultured with mesenchymal stem cells (MSC) in a hydrogel 3D system...
October 13, 2016: Oncotarget
Seyoung Seo, Jung Yong Hong, Shinkyo Yoon, Changhoon Yoo, Ji Hyun Park, Jung Bok Lee, Chan-Sik Park, Jooryung Huh, Yoonse Lee, Kyung Won Kim, Jin-Sook Ryu, Seok Jin Kim, Won Seog Kim, Dok Hyun Yoon, Cheolwon Suh
The prognostic value of serum beta-2 microglobulin for diffuse large B-cell lymphoma (DLBCL) is not well known in the rituximab era. A retrospective registry data analysis of 833 patients with de novo DLBCL treated with rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisone (R-CHOP) was conducted to establish the prognostic significance of serum beta-2 microglobulin at a ≥2.5 mg/L cutoff. Five-year progression-free survival (PFS, 76.1% vs. 41.0%; p < 0.001) and overall survival (OS, 83.8% vs...
October 18, 2016: Oncotarget
QiuShi Wei, Jin Zhang, GuoJu Hong, ZhenQiu Chen, WeiMin Deng, Wei He, Mei Hui Chen
Icariin, the main effective component of Herba Epimedii, has been identified to regulate the osteogenic differentiation of rat bone marrow stromal cells (rBMSCs) and have potential application in preventing bone loss and promoting bone regeneration. However, the underlying signaling pathway of its osteogenic effect remains unclear. Here, we investigated whether icariin could promote osteogenesis of rBMSCs through modulating the estrogen receptor alpha (ERα) and Wnt/β-catenin signaling pathways, which implicated in rBMSCs osteogenesis...
October 17, 2016: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
Hai-Juan Liu, Hua Yan, Jun Yan, Hao Li, Liang Chen, Li-Ren Han, Xiao-Fei Yang
Spinal cord injury (SCI) causes a significant amount of bone loss, which results in osteoporosis (OP). The neuropeptide substance P (SP) and SP receptors may play important roles in the pathogenesis of OP after SCI. To identify the roles of SP in the bone marrow mesenchymal stem cell derived osteoblasts (BMSC-OB) in SCI rats, we investigated the expression of neurokinin-1 receptors (NK1R) in BMSC-OB and the effects of SP on bone formation by development of BMSC-OB cultures. Sixty young male Sprague-Dawley rats were randomized into two groups: SHAM and SCI...
2016: PloS One
Mariann Gyöngyösi, Georgiana-Aura Giurgea, Bonni Syeda, Silvia Charwat, Beatrice Marzluf, Julia Mascherbauer, Andras Jakab, Abelina Zimba, Márta Sárközy, Noemi Pavo, Heinz Sochor, Senta Graf, Irene Lang, Gerald Maurer, Jutta Bergler-Klein
OBJECTIVE: The long-term (5-year) outcome of early (3-6 weeks after acute myocardial infarction [AMI], BM-MNC Early group) and late (3-4 months after AMI, BM-MNC Late group) combined (percutaneous intramyocardial and intracoronary) delivery of autologous bone marrow mononuclear cells (BM-MNCs) was evaluated in patients with ejection fractions (EF) between 30-45% post-AMI. METHODS: Major adverse cardiac and cerebrovascular events (MACCE) and hospitalization were recorded...
2016: PloS One
Gina Leisching, Ray-Dean Pietersen, Carel van Heerden, Paul van Helden, Ian Wiid, Bienyameen Baker
The distinguishing factors that characterize the host response to infection with virulent Mycobacterium tuberculosis (M.tb) are largely confounding. We present an infection study with two genetically closely related M.tb strains that have vastly different pathogenic characteristics. The early host response to infection with these detergent-free cultured strains was analysed through RNAseq in an attempt to provide information on the subtleties which may ultimately contribute to the virulent phenotype. Murine bone marrow derived macrophages (BMDMs) were infected with either a hyper- (R5527) or hypovirulent (R1507) Beijing M...
October 20, 2016: Virulence
Weiguo Cao, Changhong Liang, Yungan Gen, Chen Wang, Cailei Zhao, Longwei Sun
PURPOSE: We aimed to determine whether diffusion-weighted imaging (DWI) with apparent diffusion coefficient (ADC) measurement can detect skull bone marrow infiltration in newly diagnosed acute lymphoblastic leukemia (ALL) children before therapy and normalization in complete remission after treatment. METHODS: Fifty-one newly diagnosed acute lymphoblastic leukemia (ALL) patients and 30 healthy age-matched subjects were included. Cranial magnetic resonance imaging (MRI) scans were reviewed, and skull marrow ADC values were compared before treatment and in complete remission after therapy...
October 20, 2016: Diagnostic and Interventional Radiology: Official Journal of the Turkish Society of Radiology
Tomas Ganz
Macrophages exert multiple important roles in iron metabolism. As scavengers, splenic and hepatic macrophages phagocytize and degrade senescent and damaged erythrocytes to recycle iron, predominantly for the production of hemoglobin in new erythrocytes. Splenic red pulp macrophages are specialized for iron recycling, with increased expression of proteins for the uptake of hemoglobin, breakdown of heme, and export of iron. Iron release from macrophages is closely regulated by the interaction of hepcidin, a peptide hormone produced by hepatocytes, with the macrophage iron exporter ferroportin...
October 2016: Microbiology Spectrum
Kipp Weiskopf, Peter J Schnorr, Wendy W Pang, Mark P Chao, Akanksha Chhabra, Jun Seita, Mingye Feng, Irving L Weissman
The hematopoietic stem cell (HSC) is a multipotent stem cell that resides in the bone marrow and has the ability to form all of the cells of the blood and immune system. Since its first purification in 1988, additional studies have refined the phenotype and functionality of HSCs and characterized all of their downstream progeny. The hematopoietic lineage is divided into two main branches: the myeloid and lymphoid arms. The myeloid arm is characterized by the common myeloid progenitor and all of its resulting cell types...
October 2016: Microbiology Spectrum
Nilton Lavatori Correa, Lidia Vasconcellos de Sá, Rossana Corbo
: An increase in the incidence of second primary cancers (SPC) is the late effect of greatest concern that could occur in differentiated thyroid carcinoma (DTC) patients treated with radioactive iodine (RAI). The decision to treat a patient with RAI should therefore incorporate a careful risk-benefit analysis. The objective of this work is to adapt the risk estimation models developed by the Biological Effects of Ionizing Radiation Committee (BEIR VII) to local epidemiological characteristics, to assess the carcinogenesis risk from radiation in a population of Brazilian DTC patients treated with RAI...
October 20, 2016: Thyroid: Official Journal of the American Thyroid Association
Yuxia Yang, Yanju Zhang, Zhenchuan Miao, Junhua Zhou, Jianyuan Luo
The bone marrow (BM) microenvironment, heavily composed of osteoblasts, plays a key role during the normal development of hematopoiesis. Endogenous miR-22 has an important function on the hematopoietic development and osteoblastic differentiation. It is unclear whether miR-22 in osteoblasts from the BM microenvironment also has an important function on the development of hematopoiesis. In this study, we found that the capacity of FBMOB-hTERT cells to expand human cord blood (CB) CD34+ cells and maintain the multipotency of CB CD34+ cells is decreased upon ectopic expression of miR-22...
October 20, 2016: Human Gene Therapy
Ana Marina Ferreira, Piergiorgio Gentile, Sotiria Toumpaniari, Gianluca Ciardelli, Mark A Birch
Bone cell interaction with extracellular matrix (ECM) microenvironment is of critical importance when engineering surface interfaces for bone regeneration. In this work layer-by-layer films of type I collagen (coll), the major constituent of bone ECM, and heparin (hep), a glycosaminoglycan, were assembled on poly(L-lactide acid) (PLLA) substrates to evaluate the impact of the biomacromolecular coating on cell activity. The surface modification of PLLA demonstrated that the hep/coll multi-layer is stable after 10 bilayers (confirmed by contact angle, infrared spectroscopy and morphological analysis)...
October 20, 2016: ACS Applied Materials & Interfaces
Animesh Pardanani
: Disease overview:Systemic mastocytosis (SM) results from a clonal proliferation of abnormal mast cells (MC) in one or more extra-cutaneous organs. DIAGNOSIS: The major criterion is presence of multifocal clusters of morphologically abnormal MC in the bone marrow. Minor diagnostic criteria include elevated serum tryptase level, abnormal MC expression of CD25 and/or CD2, and presence of KITD816V. Risk stratification: The 2008 World Health Organization (WHO) classification of SM has been shown to be prognostically relevant...
November 2016: American Journal of Hematology
Joceline S Liu, Matthew I Bury, Natalie J Fuller, Renea M Sturm, Nida Ahmad, Arun K Sharma
Substitution urethroplasty for the treatment of male stricture disease is often accompanied by subsequent tissue fibrosis and secondary stricture formation. Patients with pre-existing morbidities are often at increased risk of urethral stricture recurrence brought upon in-part by delayed vascularization accompanied by overactive inflammatory responses following surgery. Within the context of this study, we demonstrate the functional utility of a cell/scaffold composite graft comprised of human bone marrow-derived mesenchymal stem cells (MSC) combined with CD34+ hematopoietic stem/progenitor cells (HSPC) to modulate inflammation and wound healing in a rodent model of substitution urethroplasty...
October 20, 2016: Scientific Reports
Jennifer E Adair, Timothy Waters, Kevin G Haworth, Sara P Kubek, Grant D Trobridge, Jonah D Hocum, Shelly Heimfeld, Hans-Peter Kiem
Haematopoietic stem cell (HSC) gene therapy has demonstrated potential to treat many diseases. However, current state of the art requires sophisticated ex vivo gene transfer in a dedicated Good Manufacturing Practices facility, limiting availability. An automated process would improve the availability and standardized manufacture of HSC gene therapy. Here, we develop a novel program for semi-automated cell isolation and culture equipment to permit complete benchtop generation of gene-modified CD34(+) blood cell products for transplantation...
October 20, 2016: Nature Communications
Mingyong Gao, Paul Lu, Dan Lynam, Bridget Bednark, W Marie Campana, Jeff Sakamoto, Mark Tuszynski
OBJECTIVE: We combined implantation of multi-channel templated agarose scaffolds with growth factor gene delivery to examine whether this combinatorial treatment can enhance peripheral axonal regeneration through long sciatic nerve gaps. APPROACH: 15 mm long scaffolds were templated into highly organized, strictly linear channels, mimicking the linear organization of natural nerves into fascicles of related function. Scaffolds were filled with syngeneic bone marrow stromal cells (MSCs) secreting the growth factor brain derived neurotrophic factor (BDNF), and lentiviral vectors expressing BDNF were injected into the sciatic nerve segment distal to the scaffold implantation site...
October 20, 2016: Journal of Neural Engineering
Dagmar Hildebrand, Katharina F Kubatzky
Flow cytometric techniques allow fast, sensitive, and multiparametric analyses at the single cell level. This makes it possible to distinguish subsets of cells within heterogeneous samples. Moreover, flow cytometry has become a frequently used method for the evaluation of therapeutic effects. Here, we describe the analysis of the phosphorylation status of signal transducer and activator of transcription-1 (STAT-1) in primary mouse cells after treatment with histone deacetylase inhibitors (HDACi) that are currently considered anticancer agents...
2017: Methods in Molecular Biology
Alberto L Horenstein, Valeria Quarona, Denise Toscani, Federica Costa, Antonella Chillemi, Vito Pistoia, Nicola Giuliani, Fabio Malavasi
Human myeloma cells express CD38 at high levels and grow in hypoxic niches inside the bone marrow. Myeloma cells respond to hypoxia with metabolic changes leading to aerobic glycolysis, thus reducing ATP and increasing NAD(+). Our hypothesis is that these conditions favor the enzymatic pathways involved in the production of adenosine in the niche. Within the niche, NAD(+) is able to activate a discontinuous adenosinergic pathway that relies upon CD38, CD203a, and CD73 or TRACP, according to the environmental pH...
October 13, 2016: Molecular Medicine
Zhong'e Zhou, Yong Tang, Xian Jin, Chengjun Chen, Yi Lu, Liang Liu, Chengxing Shen
Advanced glycation end products (AGEs) are major inflammatory mediators in diabetes, affecting atherosclerosis progression via macrophages. Metformin slows diabetic atherosclerosis progression through mechanisms that remain to be fully elucidated. The present study of murine bone marrow derived macrophages showed that (1) AGEs enhanced proinflammatory cytokines (interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α)) mRNA expression, RAGE expression, and NFκB activation; (2) metformin pretreatment inhibited AGEs effects and AGEs-induced cluster designation 86 (CD86) (M1 marker) expression, while promoting CD206 (M2 marker) surface expression and anti-inflammatory cytokine (IL-10) mRNA expression; and (3) the AMPK inhibitor, Compound C, attenuated metformin effects...
2016: Journal of Diabetes Research
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