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https://www.readbyqxmd.com/read/28074350/a-comparative-study-of-the-bone-regenerative-effect-of-chemically-modified-rna-encoding-bmp-2-or-bmp-9
#1
Behnoush Khorsand, Satheesh Elangovan, Liu Hong, Alexander Dewerth, Michael S D Kormann, Aliasger K Salem
Employing cost-effective biomaterials to deliver chemically modified ribonucleic acid (cmRNA) in a controlled manner addresses the high cost, safety concerns, and lower transfection efficiency that exist with protein and gene therapeutic approaches. By eliminating the need for nuclear entry, cmRNA therapeutics can potentially overcome the lower transfection efficiencies associated with non-viral gene delivery systems. Here, we investigated the osteogenic potential of cmRNA-encoding BMP-9, in comparison to cmRNA-encoding BMP-2...
January 10, 2017: AAPS Journal
https://www.readbyqxmd.com/read/28073305/human-amniotic-mesenchymal-stromal-cells-as-favourable-source-for-cartilage-repair
#2
Emma Muinos-López, Tamara Hermida-Gómez, Isaac Fuentes-Boquete, Francisco Javier de Toro-Santos, Francisco J Blanco, Silvia María Díaz-Prado
INTRODUCTION: Localized trauma-derived breakdown of the hyaline articular cartilage may progress towards osteoarthritis, a degenerative condition characterized by total loss of articular cartilage and joint function. Tissue engineering technologies encompass several promising approaches with high therapeutic potential for the treatment of these focal defects. However, most of the research in tissue engineering is focused on potential materials and structural cues, while little attention is directed to the most appropriate source of cells endowing these materials...
January 10, 2017: Tissue Engineering. Part A
https://www.readbyqxmd.com/read/28069556/regeneration-of-bone-using-nanoplex-delivery-of-fgf-2-and-bmp-2-genes-in-diaphyseal-long-bone-radial-defects-in-a-diabetic-rabbit-model
#3
Behnoush Khorsand, Nate Nicholson, Anh-Vu Do, John E Femino, James A Martin, Emily Petersen, Brian Guetschow, Douglas C Fredericks, Aliasger K Salem
Bone fracture healing impairment related to systemic diseases such as diabetes can be addressed by growth factor augmentation. We previously reported that growth factors such as fibroblast growth factor-2 (FGF-2) and bone morphogenetic protein-2 (BMP-2) work synergistically to encourage osteogenesis in vitro. In this report, we investigated if BMP-2 and FGF-2 together can synergistically promote bone repair in a leporine model of diabetes mellitus, a condition that is known to be detrimental to union. We utilized two kinds of plasmid DNA encoding either BMP-2 or FGF-2 formulated into polyethylenimine (PEI) complexes...
January 7, 2017: Journal of Controlled Release: Official Journal of the Controlled Release Society
https://www.readbyqxmd.com/read/28060333/mesenchymal-stromal-cell-culture-and-delivery-in-autologous-conditions-a-smart-approach-for-orthopedic-applications
#4
Luisa Trombi, Serena Danti, Sara Savelli, Stefania Moscato, Delfo D'Alessandro, Claudio Ricci, Stefano Giannotti, Mario Petrini
Human Mesenchymal Stromal Cells (hMSCs) are cultured in vitro with different media. Limits on their use in clinical settings, however, mainly depend on potential biohazard and inflammation risks exerted by xenogeneic nutrients for their culture. Human derivatives or recombinant materials are the first choice candidates to reduce these reactions. Therefore, culture supplements and materials of autologous origin represent the best nutrients and the safest products. Here, we describe a new protocol for the isolation and culture of bone marrow hMSCs in autologous conditions - namely, patient-derived serum as a supplement for the culture medium and fibrin as a scaffold for hMSC administration...
December 8, 2016: Journal of Visualized Experiments: JoVE
https://www.readbyqxmd.com/read/28049042/aryl-hydrocarbon-receptor-activation-by-2-3-7-8-tetrachlorodibenzo-p-dioxin-impairs-human-b-lymphopoiesis
#5
Jinpeng Li, Ashwini S Phadnis-Moghe, Robert B Crawford, Norbert E Kaminski
The homeostasis of peripheral B cell compartment requires lifelong B lymphopoiesis from hematopoietic stem cells (HSC). As a result, the B cell repertoire is susceptible to disruptions of hematopoiesis. Increasing evidence, primarily from rodent models, shows that the aryl hydrocarbon receptor (AHR) regulates hematopoiesis. To study the effects of persistent AHR activation on human B cell development, a potent AHR agonist and known environmental contaminant, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) was utilized...
December 31, 2016: Toxicology
https://www.readbyqxmd.com/read/28044259/bortezomib-interferes-with-adhesion-of-b-cell-precursor-acute-lymphoblastic-leukemia-cells-through-sparc-up-regulation-in-human-bone-marrow-mesenchymal-stromal-stem-cells
#6
Masaki Iwasa, Yasuo Miura, Aya Fujishiro, Sumie Fujii, Noriko Sugino, Satoshi Yoshioka, Asumi Yokota, Terutoshi Hishita, Hideyo Hirai, Akira Andoh, Tatsuo Ichinohe, Taira Maekawa
The poor prognosis of adults with B cell precursor acute lymphoblastic leukemia (BCP-ALL) is attributed to leukemia cells that are protected by the bone marrow (BM) microenvironment. In the present study, we explored the pharmacological targeting of mesenchymal stromal/stem cells in BM (BM-MSCs) to eliminate chemoresistant BCP-ALL cells. Human BCP-ALL cells (NALM-6 cells) that adhered to human BM-MSCs (NALM-6/Ad) were highly resistant to multiple anti-cancer drugs, and exhibited pro-survival characteristics, such as an enhanced Akt/Bcl-2 pathway and increased populations in the G0 and G2/S/M cell cycle stages...
January 2, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28044100/photocrosslinkable-chitosan-hydrogels-functionalized-with-the-rgd-peptide-and-phosphoserine-to-enhance-osteogenesis
#7
Soyon Kim, Zhong-Kai Cui, Jiabing Fan, Armita Fartash, Tara L Aghaloo, Min Lee
Hydrogels derived from naturally occurring polymers are attractive matrix for tissue engineering. Here, we report a biofunctional hydrogel for specific use in bone regeneration by introducing Arg-Gly-Asp (RGD)-containing cell adhesive motifs and phosphorylated serine residues, which are prevalent in native bone extracellular matrix and known to promote osteogenesis by enhancing cell-matrix interactions and hydroxyapatite nucleation, into photopolymerizable methacrylated glycol chitosan (MeGC). Incorporation of phosphoserine into MeGC hydrogels increased the ability of the hydrogels to nucleate mineral on their surfaces...
August 21, 2016: Journal of Materials Chemistry. B, Materials for Biology and Medicine
https://www.readbyqxmd.com/read/28043150/histone-deacetylase-inhibitors-in-plasma-cell-leukemia-treatment-effect-of-bone-marrow-microenvironment
#8
I Burianova, K Kuzelova, O Mitrovsky, I Spicka, P StOckbauer, M Zackova
In the presented study we analysed the effect of histone deacetylase inhibitors (HDACi) suberoylanilide hydroxamic acid (SAHA) and valproic acid (VPA) on human plasma cell leukemia (PCL) cell line UHKT-944 in the presence of bone marrow microenvironment (BMM). For the analysis, the cells were cultured alone, with bone marrow stromal cells (BMSCs), with extracellular matrix (ECM) components or with interleukin-6, and treated with varied concentrations of SAHA and VPA for 24/48 hours. To study the effect of HDACi, we investigated cell proliferation, apoptosis, cell cycle and changes in selected signalling pathways...
January 3, 2017: Neoplasma
https://www.readbyqxmd.com/read/28032590/predicting-the-impact-of-combined-therapies-on-myeloma-cell-growth-using-a-hybrid-multi-scale-agent-based-model
#9
Zhiwei Ji, Jing Su, Dan Wu, Huiming Peng, Weiling Zhao, Brian Nlong Zhao, Xiaobo Zhou
Multiple myeloma is a malignant still incurable plasma cell disorder. This is due to refractory disease relapse, immune impairment, and development of multi-drug resistance. The growth of malignant plasma cells is dependent on the bone marrow (BM) microenvironment and evasion of the host's anti-tumor immune response. Hence, we hypothesized that targeting tumor-stromal cell interaction and endogenous immune system in BM will potentially improve the response of multiple myeloma (MM). Therefore, we proposed a computational simulation of the myeloma development in the complicated microenvironment which includes immune cell components and bone marrow stromal cells and predicted the effects of combined treatment with multi-drugs on myeloma cell growth...
December 9, 2016: Oncotarget
https://www.readbyqxmd.com/read/28031234/the-multiple-roles-of-exosomes-in-metastasis
#10
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...
January 2017: Cancer Genomics & Proteomics
https://www.readbyqxmd.com/read/28031181/ibrutinib-inhibits-pre-bcr-b-cell-acute-lymphoblastic-leukemia-progression-by-targeting-btk-and-blk
#11
Ekaterina Kim, Christian Hurtz, Stefan Koehrer, Zhiqiang Wang, Sriram Balasubramanian, Betty Y Chang, Markus Müschen, R Eric Davis, Jan A Burger
Targeting B cell receptor (BCR) signaling is a successful therapeutic strategy in mature B cell malignancies. Precursor BCR (pre-BCR) signaling, which is critical during normal B lymphopoiesis, also plays an important role in pre-BCR(+) B cell acute lymphoblastic leukemia (B-ALL). Here, we investigated the activity and mechanism of action of the BTK inhibitor ibrutinib in preclinical models of B-ALL. Pre-BCR(+) ALL cells were exquisitely sensitive to ibrutinib at therapeutically relevant drug concentrations...
December 28, 2016: Blood
https://www.readbyqxmd.com/read/28030558/loss-of-trpv4-function-suppresses-inflammatory-fibrosis-induced-by-alkali-burning-mouse-corneas
#12
Yuka Okada, Kumi Shirai, Masayasu Miyajima, Peter S Reinach, Osamu Yamanaka, Takayoshi Sumioka, Masahide Kokado, Katsuo Tomoyose, Shizuya Saika
In humans suffering from pulmonary disease and a mouse model, transient receptor potential vanilloid 4 (TRPV4) channel activation contributes to fibrosis. As a corneal alkali burn induces the same response, we determined if such an effect is also attributable to TRPV4 activation in mice. Accordingly, we determined if the alkali burn wound healing responses in wild-type (WT) mice are different than those in their TRPV4-null (KO) counterpart. Stromal opacification due to fibrosis in KO (n = 128) mice was markedly reduced after 20 days relative to that in WT (n = 157) mice...
2016: PloS One
https://www.readbyqxmd.com/read/28026812/-the-hepatic-differentiation-of-adult-and-fetal-liver-stromal-cells-in-vitro
#13
I V Kholodenko, R V Kholodenko, G V Manukyan, K N Yarygin
The liver has a marked capacity for regeneration. In most cases the liver regeneration is determined by hepatocytes. The regenerative capacity of hepatocytes is significantly reduced in acute or chronic damage. In particular, repair mechanisms are not activated in patients with alcoholic cirrhosis. Organ transplantation or advanced methods of regenerative medicine can help such patients. The promising results were obtained in clinical trials involving patients with various forms of liver disease who received transplantation of autologous bone marrow stem cells...
November 2016: Biomedit︠s︡inskai︠a︡ Khimii︠a︡
https://www.readbyqxmd.com/read/28025583/a-novel-bcma-cd3-bi-specific-t-cell-engager-for-the-treatment-of-multiple-myeloma-induces-selective-lysis-in-vitro-and-in-vivo
#14
S Hipp, Y-T Tai, D Blanset, P Deegen, J Wahl, O Thomas, B Rattel, P J Adam, K Anderson, M Friedrich
B cell maturation antigen (BCMA) is a highly plasma cell selective protein that is expressed on malignant plasma cells of multiple myeloma (MM) patients and therefore is an ideal target for T cell redirecting therapies. We developed a bispecific T cell engager (BiTE(®)) targeting BCMA and CD3ɛ (BI 836909) and studied its therapeutic impacts on MM. BI 836909 induced selective lysis of BCMA-positive MM cells, activation of T cells, release of cytokines and T cell proliferation; whereas BCMA-negative cells were not affected...
December 27, 2016: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
https://www.readbyqxmd.com/read/28024632/preliminary-study-on-the-corrosion-resistance-antibacterial-activity-and-cytotoxicity-of-selective-laser-melted-ti6al4v-xcu-alloys
#15
Sai Guo, Yanjin Lu, Songquan Wu, Lingling Liu, Mengjiao He, Chaoqian Zhao, Yiliang Gan, Junjie Lin, Jiasi Luo, Xiongcheng Xu, Jinxin Lin
In this study, a series of Cu-bearing Ti6Al4V-xCu (x=0, 2, 4, 6wt%) alloys (shorten by Ti6Al4V, 2C, 4C, and 6C, respectively.) with antibacterial function were successfully fabricated by selective laser melting (SLM) technology with mixed spherical powders of Cu and Ti6Al4V for the first time. In order to systematically investigate the effects of Cu content on the microstructure, phase constitution, corrosion resistance, antibacterial properties and cytotoxicity of SLMed Ti6Al4V-xCu alloys, experiments including XRD, SEM-EDS, electrochemical measurements, antibacterial tests and cytotoxicity tests were conducted with comparison to SLMed Ti6Al4V alloy (Ti6Al4V)...
March 1, 2017: Materials Science & Engineering. C, Materials for Biological Applications
https://www.readbyqxmd.com/read/28024509/-effects-of-different-culture-systems-on-the-hematopoietic-differentiation-ability-of-ips-cells
#16
Di Fan, Wen-Yin He, Xiao-Hua Niu, Zhan-Hui Ou, Yu-Chang Chen, Xiao-Fang Sun
OBJECTIVE: To investigate the in vitro effects of different culture systems on hematopoietic differentiation ability of induced pluripotent stem (iPS) cells. METHOD: Two culture systems including E8 and mTESR(freeder-free medium), and the classical ES culture medium were chosen for culture of iPS cells. The iPS cells maintaining in above mentioning culcure systems were co-cultured with OP9 cells(murine bone marrow stromal cells) in vitro to be induced to differentiate into hematopoietic stem/progenitor cells...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28024469/-role-of-non-classical-nf-%C3%AE%C2%BAb-signaling-pathway-in-b-acute-lymphoblastic-leukemia
#17
Xiao-Lei Liu, Yi Cai, Bao-Jing Li, Wei-Bo Huang
OBJECTIVE: To study the role of non-classical NF-κB signaling pathway in B acute lymphoblastic leukemia (B-ALL). METHODS: The bone marrow samples from 48 patients with B-ALL were collected from March 2015 to March 2016. The real-time quantitative RT-PCR was used for determing mRNA expression levels of NF-κB family members; the NF-κB DNA binding activity in B-ALL cell nucleus was analyzed by ELISA; the apoptosis rate of B-ALL cells alone or co-cultured with bone marrow stromal cells (hBMSC) was determined by flow cytometry...
December 2016: Zhongguo Shi Yan Xue Ye Xue za Zhi
https://www.readbyqxmd.com/read/28019696/crmp4-inhibits-bone-formation-by-negatively-regulating-bmp-and-rhoa-signaling
#18
Basem M Abdallah, Florence Figeac, Kenneth H Larsen, Nicholas Ditzel, Pankaj Keshari, Adiba Isa, Abbas Jafari, Thomas L Andersen, Jean-Marie Delaisse, Yoshio Goshima, Toshio Ohshima, Moustapha Kassem
We identified the neuro-protein CRMP4 (collapsing response mediator protein-4) as a non-canonical osteogenic factor that regulating the differentiation of mouse bone marrow skeletal stem cells (bone marrow stromal stem cells, mBMSCs) into osteoblastic cells. CRMP4 is the only member of the CRMP 1-5 family to be expressed by mBMSCs and in osteoprogenitors of both adult mouse and human bones. In vitro gain and loss function of CRMP4 in murine stromal cells revealed its inhibitory effect on osteoblast differentiation...
December 26, 2016: Journal of Bone and Mineral Research: the Official Journal of the American Society for Bone and Mineral Research
https://www.readbyqxmd.com/read/28017598/biodegradable-poly-%C3%AE%C2%B5-caprolactone-microcarriers-for-efficient-production-of-human-mesenchymal-stromal-cells-and-secreted-cytokines-in-batch-and-fed-batch-bioreactors
#19
Alan Tin-Lun Lam, Jian Li, Jessica Pei-Wen Toh, Eileen Jia-Hui Sim, Allen Kuan-Liang Chen, Jerry Kok-Yen Chan, Mahesh Choolani, Shaul Reuveny, William R Birch, Steve Kah-Weng Oh
Large numbers of human mesenchymal stromal cells (MSCs) used for a variety of applications in tissue engineering and cell therapy can be generated by scalable expansion in a bioreactor using microcarriers (MCs) systems. However, the enzymatic digestion process needed to detach cells from the growth surface can affect cell viability and potentially the potency and differentiation efficiency. Thus, the main aim of our study was to develop biocompatible and biodegradable MCs that can support high MSC yields while maintaining their differentiation capability and potency...
December 22, 2016: Cytotherapy
https://www.readbyqxmd.com/read/28012456/comparative-phenotypic-transcriptional-characterization-of-human-full-term-placenta-derived-mesenchymal-stromal-cells-compared-to-bone-marrow-derived-mesenchymal-stromal-cells-after-differentiation-in-myogenic-medium
#20
Melanie L Hart, Marvin Kaupp, Juliane Brun, Wilhelm K Aicher
Placenta-derived mesenchymal stromal cells (pMSCs) are a very attractive source of MSCs. In this short report we evaluated the expression of phenotypic markers from fetal and maternal pMSCs after exposure to myogenic medium commonly used to differentiate bone marrow MSCs (bmMSCs) to smooth muscle-like cells (SMCs). In order to reveal differences between these different MSC sources, cells were expanded and differentiated to elucidate whether this differentiation protocol facilitated efficient differentiation of SMCs from human pMSCs...
January 2017: Placenta
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