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https://www.readbyqxmd.com/read/28818982/sf3b1-mutation-arises-at-the-multipotent-hsc-level
#1
(no author information available yet)
No abstract text is available yet for this article.
August 17, 2017: Blood
https://www.readbyqxmd.com/read/28817720/targeting-of-cdk9-with-indirubin-3-monoxime-safely-and-durably-reduces-hiv-viremia-in-chronically-infected-humanized-mice
#2
Sandra Medina-Moreno, Thomas C Dowling, Juan C Zapata, Nhut M Le, Edward Sausville, Joseph Bryant, Robert R Redfield, Alonso Heredia
Successful propagation of HIV in the human host requires entry into a permissive cell, reverse transcription of viral RNA, integration into the human genome, transcription of the integrated provirus, and assembly/release of new virus particles. Currently, there are antiretrovirals against each of these viral steps, except for provirus transcription. An inhibitor of HIV transcription could both increase potency of treatment and suppress drug-resistant strains. Cellular cyclin-dependent kinase 9 (CDK9) serves as a cofactor for the HIV Tat protein and is required for effective transcription of the provirus...
2017: PloS One
https://www.readbyqxmd.com/read/28816065/improved-hematopoietic-gene-therapy-in-a-mouse-model-of-fanconi-anemia-mediated-by-mesenchymal-stromal-cells
#3
Maria Fernandez-Garcia, Maria Lamana Luzuriaga, Miriam Hernando-Rodriguez, Rebeca Sanchez-Dominguez, Juan Bueren, Rosa Yañez
In this study we propose a novel approach based on the use of mesenchymal stromal cells (MSC) aiming at limiting risks of graft failure in gene therapy protocols associated with low conditioning regimens. Because the engraftment of corrected hematopoietic stem cells (HSCs) is particularly challenging in Fanconi anemia (FA), we have investigated the relevance of MSCs in an experimental model of FA gene therapy. Our results firstly showed that risks of graft failure in recipients conditioned with a moderate dose of 5Gy and infused with limited numbers of WT HSCs are significantly higher in Fanca-/- recipients as compared to WT recipients...
August 17, 2017: Human Gene Therapy
https://www.readbyqxmd.com/read/28815178/stem-cell-manipulation-gene-therapy-and-the-risk-of-cancer-stem-cell-emergence
#4
REVIEW
Flora Clément, Elodie Grockowiak, Florence Zylbersztejn, Gaëlle Fossard, Stéphanie Gobert, Véronique Maguer-Satta
Stem cells (SCs) have been extensively studied in the context of regenerative medicine. Human hematopoietic stem cell (HSC)-based therapies have been applied to treat leukemic patients for decades. Handling of mesenchymal stem cells (MSCs) has also raised hopes and concerns in the field of tissue engineering. Lately, discovery of cell reprogramming by Yamanaka's team has profoundly modified research strategies and approaches in this domain. As we gain further insight into cell fate mechanisms and identification of key actors and parameters, this also raises issues as to the manipulation of SCs...
2017: Stem Cell Investigation
https://www.readbyqxmd.com/read/28814957/induced-pluripotent-stem-cell-for-the-study-and-treatment-of-sickle-cell-anemia
#5
Luiza Cunha Junqueira Reis, Virgínia Picanço-Castro, Bárbara Cristina Martins Fernandes Paes, Olívia Ambrozini Pereira, Isabela Gerdes Gyuricza, Fabiano Tófoli de Araújo, Mariana Morato-Marques, Lílian Figueiredo Moreira, Everton de Brito Oliveira Costa, Tálita Pollyanna Moreira Dos Santos, Dimas Tadeu Covas, Lygia da Veiga Pereira Carramaschi, Elisa Maria de Sousa Russo
Sickle cell anemia (SCA) is a monogenic disease of high mortality, affecting millions of people worldwide. There is no broad, effective, and safe definitive treatment for SCA, so the palliative treatments are the most used. The establishment of an in vitro model allows better understanding of how the disease occurs, besides allowing the development of more effective tests and treatments. In this context, iPSC technology is a powerful tool for basic research and disease modeling, and a promise for finding and screening more effective and safe drugs, besides the possibility of use in regenerative medicine...
2017: Stem Cells International
https://www.readbyqxmd.com/read/28813413/polylox-barcoding-reveals-haematopoietic-stem-cell-fates-realized-in-vivo
#6
Weike Pei, Thorsten B Feyerabend, Jens Rössler, Xi Wang, Daniel Postrach, Katrin Busch, Immanuel Rode, Kay Klapproth, Nikolaus Dietlein, Claudia Quedenau, Wei Chen, Sascha Sauer, Stephan Wolf, Thomas Höfer, Hans-Reimer Rodewald
Developmental deconvolution of complex organs and tissues at the level of individual cells remains challenging. Non-invasive genetic fate mapping has been widely used, but the low number of distinct fluorescent marker proteins limits its resolution. Much higher numbers of cell markers have been generated using viral integration sites, viral barcodes, and strategies based on transposons and CRISPR-Cas9 genome editing; however, temporal and tissue-specific induction of barcodes in situ has not been achieved. Here we report the development of an artificial DNA recombination locus (termed Polylox) that enables broadly applicable endogenous barcoding based on the Cre-loxP recombination system...
August 16, 2017: Nature
https://www.readbyqxmd.com/read/28811860/the-apelin-receptor-apj-in-hematopoietic-stem-cells-progenitor-cells-in-the-early-stage-of-non-alcoholic-steatohepatitis
#7
Wataru Ando, Hiroaki Yokomori, Katsuya Otori, Masaya Oda
BACKGROUND: Non-alcoholic steatohepatitis (NASH) is characterized by hepatic steatosis and inflammation with or without fibrosis. The apelin receptor (APJ) is related to angiotensin-like-receptor 1 (AGTRL1). The present study aimed to evaluate APJ as an indicator of the pathophysiology of early-stage NASH. METHODS: APJ expression was evaluated in six tissue samples with histologically proven early-stage NASH using immunohistochemistry (IHC) and immunoelectron microscopy (IEM)...
September 2017: Journal of Clinical Medicine Research
https://www.readbyqxmd.com/read/28810546/changes-in-cell-junctions-induced-by-inhibition-of-epidermal-growth-factor-receptor-in-oral-squamous-cell-carcinoma-cells
#8
Yasumasa Kakei, Shun Teraoka, Masaya Akashi, Takumi Hasegawa, Takahide Komori
The benefits of epidermal growth factor receptor (EGFR) targeting in the treatment of head and neck cancer, have been documented. However, a minority of patients with head and neck cancer are unresponsive to EGFR targeting therapies. The present study evaluated the effects and limitations of an EGFR inhibitor on oral squamous cell carcinoma cells, particularly on cell-cell junctions mediated by epithelial (E)-cadherin. HSC-3 oral squamous cell carcinoma cells were treated with the EGFR inhibitor, AG1478 (0, 0...
August 2017: Experimental and Therapeutic Medicine
https://www.readbyqxmd.com/read/28808179/aggf1-attenuates-hepatic-inflammation-and-activation-of-hepatic-stellate-cells-by-repressing-ccl2-transcription
#9
Wenping Xu, Sheng Zeng, Min Li, Zhiwen Fan, Bisheng Zhou
Liver injury represents a continuum of pathophysiological processes involving a complex interplay between hepatocytes, macrophages, and hepatic stellate cells. The mechanism whereby these intercellular interactions contribute to liver injury and fibrosis is not completely understood. We report here that angiogenic factor with G patch and FHA domains 1 (Aggf1) was downregulated in the livers of cirrhotic patients compared to healthy controls and in primary hepatocytes in response to carbon tetrachloride (CCl4) stimulation...
October 17, 2016: Journal of Biomedical Research
https://www.readbyqxmd.com/read/28807497/characterisation-of-the-porcine-cytokines-which-activate-the-cd131%C3%AE-c-common-sub-unit-for-potential-immune-augmentation
#10
G Stephenson, K R Morris, T E O'Neil, M P Bruce, A D G Strom, A G D Bean
Early acting cytokines and growth factors such as those of the CD131 βc subunit, may offer an alternative method to the current use of antibiotics and chemicals such as anthelmintics in maintaining Porcine (Po) health. Thus far, the recombinant Po (rPo) Granulocyte-macrophage colony-stimulating factor (GM-CSF), rPo interleukin-3 (IL-3) and rPo interleukin-5 (IL-5) proteins have been identified and cloned and the biological activity of each cytokine has been confirmed in vitro, however, in vivo immune system regulation and hematopoietic stem cell (HSC) augmentation are regulated by numerous cytokines and cellular signals within the bone marrow (BM) niche...
August 11, 2017: Cytokine
https://www.readbyqxmd.com/read/28806273/the-changing-landscape-of-gene-editing-in-hematopoietic-stem-cells-a-step-towards-cas9-clinical-translation
#11
Daniel P Dever, Matthew H Porteus
PURPOSE OF REVIEW: Since the discovery two decades ago that programmable endonucleases can be engineered to modify human cells at single nucleotide resolution, the concept of genome editing was born. Now these technologies are being applied to therapeutically relevant cell types, including hematopoietic stem cells (HSC), which possess the power to repopulate an entire blood and immune system. The purpose of this review is to discuss the changing landscape of genome editing in hematopoietic stem cells (GE-HSC) from the discovery stage to the preclinical stage, with the imminent goal of clinical translation for the treatment of serious genetic diseases of the blood and immune system...
August 12, 2017: Current Opinion in Hematology
https://www.readbyqxmd.com/read/28805509/enhanced-cell-killing-and-apoptosis-of-oral-squamous-cell-carcinoma-cells-with-ultrasound-in-combination-with-cetuximab-coated-albumin-microbubbles
#12
Kyoichi Narihira, Akiko Watanabe, Hong Sheng, Hitomi Endo, Loreto B Feril, Yutaka Irie, Koichi Ogawa, Seyedeh Moosavi-Nejad, Seiji Kondo, Toshihiro Kikuta, Katsuro Tachibana
Targeted microbubbles has the potential to be used for ultrasound (US) therapy and diagnosis of various cancers. In the present study, US was irradiated to oral squamous cell carcinoma cells (HSC-2) in the presence of cetuximab coated albumin microbubbles (CCAM). Cell killing rate with ultrasound treatment at 0.9W/cm(2) and 1.0W/cm(2) in the presence of CCAM was greater compared to non-targeted albumin microbubbles (p < 0.05). On the other hand, selective cell killing was not observed in human myelomonocytic lymphoma cell line (U937) that had no affinity to cetuximab...
August 14, 2017: Journal of Drug Targeting
https://www.readbyqxmd.com/read/28804632/the-pattern-of-il-24-mda-7-and-its-cognate-receptors-expression-following-activation-of-human-hepatic-stellate-cells
#13
Iman Jamhiri, Seyed Younes Hosseini, Davood Mehrabani, Zahra Khodabandeh, Ramin Yaghobi, Razieh Dowran, Saber Zahri
Activation of hepatic stellate cells (HSCs) is the pivotal event during liver fibrosis. Interleukin (IL)-24/melanoma differentiation-associated gene-7 (mda-7) has attracted attention in the pathophysiology of some diseases, while its role in activation/suppression of human HSCs is still unclear. It is important to elucidate whether the expression levels of the IL-24/mda-7 protein and its receptors in HSC cells are changed following activation. LX-2 cells, a human hepatic stellate cell line were activated by a combination of leptin and serum starvation...
August 2017: Biomedical Reports
https://www.readbyqxmd.com/read/28803234/rna-sequencing-and-bioinformatics-analysis-implicate-the-regulatory-role-of-a-long-noncoding-rna-mrna-network-in-hepatic-stellate-cell-activation
#14
Can-Jie Guo, Xiao Xiao, Li Sheng, Lili Chen, Wei Zhong, Hai Li, Jing Hua, Xiong Ma
BACKGROUND/AIMS: To analyze the long noncoding (lncRNA)-mRNA expression network and potential roles in rat hepatic stellate cells (HSCs) during activation. METHODS: LncRNA expression was analyzed in quiescent and culture-activated HSCs by RNA sequencing, and differentially expressed lncRNAs verified by quantitative reverse transcription polymerase chain reaction (qRT-PCR) were subjected to bioinformatics analysis. In vivo analyses of differential lncRNA-mRNA expression were performed on a rat model of liver fibrosis...
August 11, 2017: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/28802097/heat-shock-protein-47-effects-on-hepatic-stellate-cell-associated-receptors-in-hepatic-fibrosis-of-schistosoma-japonicum-infected-mice
#15
Yumin Zhao, Zhisheng Dang, Shuo Xu, Shigui Chong
The study aimed to explore the regulation of heat shock protein 47 (HSP47) on expressions of receptors associated with hepatic stellate cell (HSC) in liver fibrosis mouse models induced by Schistosoma japonicum (S. japonicum). Mouse fibroblasts (NIH/3T3) were transfected with HSP47 shRNA plasmid by lipofectamine transfection, and experimental fibrosis in HSCs was studied in S. japonicum mouse models treated with HSP47 shRNA in vivo. HSP47 expression was assessed using Western blot and real-time PCR. Flow cytometry was adopted to determine the expression of cell membrane receptors...
August 28, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28801972/brief-report-a-differential-transcriptomic-profile-of-ex-vivo-expanded-adult-human-hematopoietic-stem-cells-empowers-them-for-engraftment-better-than-their-surface-phenotype
#16
Nikoletta Psatha, Grigorios Georgolopoulos, Susan Phelps, Thalia Papayannopoulou
Transplantation of small cord blood (CB) units, or of autologous ex vivo-genetically modified adult hematopoietic stem cells (HSC), face the common challenge of suboptimal HSC doses for infusion and impaired engraftment of the transplanted cells. Ex vivo expansion of HSCs, using either cell-based coculture approaches or especially small molecules have been successfully tested mainly in CB and in prolonged cultures. Here, we explored whether innovative combinations of small molecules can sufficiently, after short culture, expand adult HSCs while retaining their functionality in vivo...
August 11, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28801610/creb3l2-mediated-expression-of-sec23a-sec24d-is-involved-in-hepatic-stellate-cell-activation-through-er-golgi-transport
#17
Shotaro Tomoishi, Shinichi Fukushima, Kentaro Shinohara, Toshiaki Katada, Kota Saito
Hepatic fibrosis is caused by exaggerated wound healing response to chronic injury, which eventually leads to hepatic cirrhosis. Differentiation of hepatic stellate cells (HSCs) to myofibroblast-like cells by inflammatory cytokines is the critical step in fibrosis. This step is accompanied by enlargement of the endoplasmic reticulum (ER) and Golgi apparatus, suggesting that protein synthesis and secretion are augmented in the activated HSCs. However, the process of rearrangement of secretory organelles and their functions remain to be fully elucidated...
August 11, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28801449/engraftment-and-in-vivo-proliferation-advantage-of-gene-corrected-mobilized-cd34-cells-from-fanconi-anemia-patients
#18
Paula Río, Susana Navarro, Guillermo Guenechea, Rebeca Sánchez-Domínguez, Maria Luisa Lamana, Rosa Yañez, Jose A Casado, Parinda A Mehta, Maria Roser Pujol, Jordi Surrallés, Sabine Charrier, Anne Galy, José C Segovia, Cristina Díaz de Heredia, Julián Sevilla, Juan Bueren
Previous Fanconi anemia (FA) gene therapy studies have failed to demonstrate engraftment of gene corrected hematopoietic stem and progenitor cells (HSPC) from FA patients, either after autologous transplantation or infusion into immunodeficient mice. In this study we demonstrate that a validated short transduction protocol of G-CSF plus plerixafor-mobilized CD34(+) cells from FA-A patients with a therapeutic FANCA-lentiviral vector corrects the phenotype of in vitro cultured hematopoietic progenitor cells. Transplantation of transduced FA CD34(+) cells into immunodeficient mice resulted in reproducible engraftment of myeloid, lymphoid and CD34(+) cells...
August 11, 2017: Blood
https://www.readbyqxmd.com/read/28801069/hsc-niche-biology-and-hsc-expansion-ex-vivo
#19
REVIEW
Sachin Kumar, Hartmut Geiger
Hematopoietic stem cell (HSC) transplantation can restore a new functional hematopoietic system in recipients in cases where the system of the recipient is not functional or for example is leukemic. However, the number of available donor HSCs is often too low for successful transplantation. Expansion of HSCs and thus HSC self-renewal ex vivo would greatly improve transplantation therapy in the clinic. In vivo, HSCs expand significantly in the niche, but establishing protocols that result in HSC expansion ex vivo remains challenging...
August 8, 2017: Trends in Molecular Medicine
https://www.readbyqxmd.com/read/28794616/schisandrin-b-attenuates-ccl4-induced-liver-fibrosis-in-rats-by-regulation-of-nrf2-are-and-tgf-%C3%AE-smad-signaling-pathways
#20
Qingshan Chen, Hai Zhang, Yan Cao, Ying Li, Sen Sun, Junping Zhang, Guoqing Zhang
Liver fibrosis is a major pathological feature of chronic liver diseases and there is no effective therapy program at present. Schisandrin B (Sch B) is the major bioactive ingredient of Schisandra chinensis, with antioxidative, anti-inflammatory, antitumor, and hepatoprotective properties. This study aimed to investigate the protective effect and related molecular mechanism of Sch B against carbon tetrachloride (CCl4)-induced liver fibrosis in rats. The in vivo therapeutic effect of Sch B on liver fibrosis induced by CCl4 was examined in rats...
2017: Drug Design, Development and Therapy
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