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https://www.readbyqxmd.com/read/28720126/a-small-molecule-cytokine-combination-enhances-hematopoietic-stem-cell-proliferation-via-inhibition-of-cell-differentiation
#1
Lan Wang, Xin Guan, Huihui Wang, Bin Shen, Yu Zhang, Zhihua Ren, Yupo Ma, Xinxin Ding, Yongping Jiang
BACKGROUND: Accumulated evidence supports the potent stimulating effects of multiple small molecules on the expansion of hematopoietic stem cells (HSCs) which are important for the therapy of various hematological disorders. Here, we report a novel, optimized formula, named the SC cocktail, which contains a combination of three such small molecules and four cytokines. METHODS: Small-molecule candidates were individually screened and then combined at their optimal concentration with the presence of cytokines to achieve maximum capacity for stimulating the human CD34(+) cell expansion ex vivo...
July 18, 2017: Stem Cell Research & Therapy
https://www.readbyqxmd.com/read/28714970/bone-marrow-adipocytes-promote-the-regeneration-of-stem-cells-and-haematopoiesis-by-secreting-scf
#2
Bo O Zhou, Hua Yu, Rui Yue, Zhiyu Zhao, Jonathan J Rios, Olaia Naveiras, Sean J Morrison
Endothelial cells and leptin receptor(+) (LepR(+)) stromal cells are critical sources of haematopoietic stem cell (HSC) niche factors, including stem cell factor (SCF), in bone marrow. After irradiation or chemotherapy, these cells are depleted while adipocytes become abundant. We discovered that bone marrow adipocytes synthesize SCF. They arise from Adipoq-Cre/ER(+) progenitors, which represent ∼5% of LepR(+) cells, and proliferate after irradiation. Scf deletion using Adipoq-Cre/ER inhibited haematopoietic regeneration after irradiation or 5-fluorouracil treatment, depleting HSCs and reducing mouse survival...
July 17, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28714470/essential-role-of-fbxl5-mediated-cellular-iron-homeostasis-in-maintenance-of-hematopoietic-stem-cells
#3
Yoshiharu Muto, Masaaki Nishiyama, Akihiro Nita, Toshiro Moroishi, Keiichi I Nakayama
Hematopoietic stem cells (HSCs) are maintained in a hypoxic niche to limit oxidative stress. Although iron elicits oxidative stress, the importance of iron homeostasis in HSCs has been unknown. Here we show that iron regulation by the F-box protein FBXL5 is required for HSC self-renewal. Conditional deletion of Fbxl5 in mouse HSCs results in cellular iron overload and a reduced cell number. Bone marrow transplantation reveals that FBXL5-deficient HSCs are unable to reconstitute the hematopoietic system of irradiated recipients as a result of stem cell exhaustion...
July 17, 2017: Nature Communications
https://www.readbyqxmd.com/read/28713909/effects-of-lentiviral-vector%C3%A2-mediated-shrna-silencing-of-tgf%C3%AE-1-on-the-expression-of-col1a1-in-rat-hepatic-stellate-cells
#4
Gan-Ping Bai, Guo-He Yan, Guo-Jian Wang, Ping Wan, Xiao-Fei Liu, Heng Wang, Rong-Hua Zhang
The present study aimed to construct a lentiviral RNA interference (RNAi) vector targeting the transforming growth factor β1 (TGFβ1) gene of rats, in order to examine its effect on silencing of the TGFβ1 gene and on the expression of collagen type 1 α1 (Col1a1) in HSC‑T6 rat hepatic stellate cells. Three RNAi sites of the TGFβ1 gene were selected according to its CDs sequence. Three pairs of small interfering RNA (siRNA) of these RNAi sites were synthesized and then transfected into HSC‑T6 cells, respectively, to confirm the optimal siRNA sequence via reverse transcription‑polymerase chain reaction analysis...
July 6, 2017: Molecular Medicine Reports
https://www.readbyqxmd.com/read/28713379/op9-feeder-cells-are-superior-to-m2-10b4-cells-for-the-generation-of-mature-and-functional-natural-killer-cells-from-umbilical-cord-hematopoietic-progenitors
#5
Lara Herrera, Juan Manuel Salcedo, Silvia Santos, Miguel Ángel Vesga, Francisco Borrego, Cristina Eguizabal
Adoptive natural killer (NK) cell therapy relies on the acquisition of large numbers of mature and functional NK cells. An option for future immunotherapy treatments is to use large amounts of NK cells derived and differentiated from umbilical cord blood (UCB) CD34(+) hematopoietic stem cells (HSCs), mainly because UCB is one of the most accessible HSC sources. In our study, we compared the potential of two stromal cell lines, OP9 and M2-10B4, for in vitro generation of mature and functional CD56(+) NK cells from UCB CD34(+) HSC...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28712391/-hepatic-stellate-cells-inhibit-the-proliferation-and-invasion-of-hepg2-hepatocellular-carcinoma-via-activating-%C3%AE-%C3%AE-t-cells
#6
Kai Fan, Rui Liao, Yuxiao Xie, Cong Peng, Chengyou Du
Objective To investigate the effects of γδ T cells co-cultured with human hepatic stellate cells (HSCs) on the proliferation and invasion of hepatocellular carcinoma (HCC) cells. Methods Peripheral γδ T cells of healthy volunteers and HCC patients were separated and collected by density gradient centrifugation and flow cytometry. Transwell(TM) chambers were used to co-culture LX-2 cells and γδ T cells. The concentration of IFN-γ in γδ T cell supernatant was detected by ELISA. The proliferation of HepG2 cells was analyzed by CCK-8 assay, and the invasion ability of HepG2 cells was evaluated by Transwell(TM) chamber assay...
July 2017: Xi Bao Yu Fen Zi Mian Yi Xue za Zhi, Chinese Journal of Cellular and Molecular Immunology
https://www.readbyqxmd.com/read/28712386/neuropeptide-y-improves-cisplatin-induced-bone-marrow-dysfunction-without-blocking-chemotherapeutic-efficacy-in-a-cancer-mouse-model
#7
Min Hee Park, In Kyung Jung, Woo-Kie Min, Jin Ho Choi, Gyu Man Kim, Hee Kyung Jin, Jae-Sung Bae
Cisplatin is the most effective and widely used chemotherapeutic agent for many types of cancer. Unfortunately, its clinical use is limited by its adverse effects, notably bone marrow suppression leading to abnormal hematopoiesis. We previously revealed that neuropeptide Y (NPY) is responsible for the maintenance of hematopoietic stem cell (HSC) function by protecting the sympathetic nervous system (SNS) fibers survival from chemotherapy-induced bone marrow impairment. Here, we show the NPY-mediated protective effect against bone marrow dysfunction due to cisplatin in an ovarian cancer mouse model...
July 17, 2017: BMB Reports
https://www.readbyqxmd.com/read/28711452/hematopoietic-stem-cell-transplantation-in-algeria
#8
REVIEW
M A Bekadja, M Brahimi, S Osmani, N Yafour, A Krim, F Serradj, S Talhi, K Amani, R Bouhass
Algeria is a country of 40.4 million inhabitants half of whom are younger than 30years. In Algeria, healthcare insurance covers 90% of the population. Healthcare is free and it is supported by the Ministry of Health. Sixteen university hospitals exist in Algeria and only two (Algiers and Oran) practice bone marrow transplant. Hematologic malignancies in adults account for 10% (∼4000 new cases/y) of the malignancy affecting in most cases young patients under 65years of age. In 2016, 270 transplants were performed (Algiers and Oran), including 149 allografts (related donor transplants: 99%) and 121 autografts...
July 11, 2017: Hematology/oncology and Stem Cell Therapy
https://www.readbyqxmd.com/read/28710903/stellate-cells-orchestrate-concanavalin-a-induced-acute-liver-damage
#9
Richa Rani, Ashish Tandon, Jiang Wang, Sudhir Kumar, Chandrashekhar R Gandhi
Concanavalin A (ConA) causes immune cell-mediated liver damage, but the contribution of resident nonparenchymal cells is also evident. Hepatic stellate cells (HSCs) induce hepatic inflammation and immunological reactions; we therefore investigated their role in ConA-induced liver injury. ConA was administered i.v. to control or HSC-depleted mice; hepatic histopathology and cytokines/chemokines were determined after 6 hours. In vitro, the effects of ConA-conditioned HSC medium on hepatocytes were determined...
July 12, 2017: American Journal of Pathology
https://www.readbyqxmd.com/read/28710180/dipeptidyl-peptidase-4-regulates-hematopoietic-stem-cell-activation-in-response-to-chronic-stress
#10
Enbo Zhu, Lina Hu, Hongxian Wu, Limei Piao, Guangxian Zhao, Aiko Inoue, Weon Kim, Chenglin Yu, Wenhu Xu, Yasuko K Bando, Xiang Li, Yanna Lei, Chang-Ning Hao, Kyosuke Takeshita, Woo-Shik Kim, Kenji Okumura, Toyoaki Murohara, Masafumi Kuzuya, Xian Wu Cheng
BACKGROUND: DPP4 (Dipeptidyl peptidase-4)-GLP-1 (glucagon-like peptide-1) and its receptor (GLP-1R) axis has been involved in several intracellular signaling pathways. The Adrβ3 (β3-adrenergic receptor)/CXCL12 (C-X-C motif chemokine 12) signal was required for the hematopoiesis. We investigated the novel molecular requirements between DPP4-GLP-1/GLP-1 and Adrβ3/CXCL12 signals in bone marrow (BM) hematopoietic stem cell (HSC) activation in response to chronic stress. METHODS AND RESULTS: Male 8-week-old mice were subjected to 4-week intermittent restrain stress and orally treated with vehicle or the DPP4 inhibitor anagliptin (30 mg/kg per day)...
July 14, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28707218/the-dna-damage-response-pathway-in-normal-hematopoiesis-and-malignancies
#11
REVIEW
Domenico Delia, Shuki Mizutani
In mammalian cells, the DNA damage response (DDR) prevents the replication and propagation of DNA errors to the next generation, thus maintaining genomic stability. At the heart of the DDR are the related signaling kinases ATM, ATR, and DNA-PK, which regulate DNA repair and associated events such as cell cycle checkpoints, chromatin remodeling, transcription, and ultimately apoptosis. Several findings highlight the occurrence of DDR in hemopoietic stem cells (HSCs), and persistence of DNA lesions in these cells promotes their functional decline and accumulation of leukemogenic mutations...
July 13, 2017: International Journal of Hematology
https://www.readbyqxmd.com/read/28702683/blood-on-the-tracks-hematopoietic-stem-cell-endothelial-cell-interactions-in-homing-and-engraftment
#12
REVIEW
Julie R Perlin, Audrey Sporrij, Leonard I Zon
Cells of the hematopoietic system undergo rapid turnover. Each day, humans require the production of about one hundred billion new blood cells for proper function. Hematopoietic stem cells (HSCs) are rare cells that reside in specialized niches and are required throughout life to produce specific progenitor cells that will replenish all blood lineages. There is, however, an incomplete understanding of the molecular and physical properties that regulate HSC migration, homing, engraftment, and maintenance in the niche...
August 2017: Journal of Molecular Medicine: Official Organ of the "Gesellschaft Deutscher Naturforscher und Ärzte"
https://www.readbyqxmd.com/read/28702667/microengineered-cultures-containing-human-hepatic-stellate-cells-and-hepatocytes-for-drug-development
#13
Matthew D Davidson, David A Kukla, Salman R Khetani
In non-alcoholic steatohepatitis (NASH), hepatic stellate cells (HSC) differentiate into myofibroblast-like cells that cause fibrosis, which predisposes patients to cirrhosis and hepatocellular carcinoma. Thus, modeling interactions between activated HSCs and hepatocytes in vitro can aid in the development of anti-NASH/fibrosis therapeutics and lead to a better understanding of disease progression. Species-specific differences in drug metabolism and disease pathways now necessitate the supplementation of animal studies with data acquired using human liver models; however, current models do not adequately model the negative effects of primary human activated HSCs on the phenotype of otherwise well-differentiated primary human hepatocytes (PHHs) as in vivo...
July 12, 2017: Integrative Biology: Quantitative Biosciences From Nano to Macro
https://www.readbyqxmd.com/read/28702135/effect-of-tgf-%C3%AE-smad-signaling-pathway-blocking-on-expression-profiles-of-mir-335-mir-150-mir-194-mir-27a-and-mir-199a-of-hepatic-stellate-cells-hscs
#14
Parivash Davoodian, Mehrdad Ravanshad, Seyed Younes Hosseini, Sayyad Khanizadeh, Mohammad Almasian, Azim Nejati Zadeh, Hamed Esmaiili Lashgarian
AIM: The aim of this study was to determine the effect of inhibition of TGF-β/smad signaling on the expression profiles of miR-335, miR-150, miR-194, miR-27a, miR-199a of hepatic stellate cells (HSCs). BACKGROUND: Liver fibrosis is excessive deposition of extracellular matrix proteins due to ongoing inflammation and HSC activation that occurs in most types of chronic liver diseases. Recent studies have shown the importance of microRNAs in the pathogenesis of chronic liver diseases...
2017: Gastroenterology and Hepatology From Bed to Bench
https://www.readbyqxmd.com/read/28701883/20s-protopanaxadiol-an-aglycosylated-ginsenoside-metabolite-induces-hepatic-stellate-cell-apoptosis-through-liver-kinase-b1-amp-activated-protein-kinase-activation
#15
Sang Mi Park, Eun Hye Jung, Jae Kwang Kim, Kyung Hwan Jegal, Chung A Park, Il Je Cho, Sang Chan Kim
BACKGROUND: Previously, we reported that Korean Red Ginseng inhibited liver fibrosis in mice and reduced the expressions of fibrogenic genes in hepatic stellate cells (HSCs). The present study was undertaken to identify the major ginsenoside responsible for reducing the numbers of HSCs and the underlying mechanism involved. METHODS: Using LX-2 cells (a human immortalized HSC line) and primary activated HSCs, MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide) assays were conducted to examine the cytotoxic effects of ginsenosides...
July 2017: Journal of Ginseng Research
https://www.readbyqxmd.com/read/28700350/thymosin-%C3%AE-4-inhibits-proliferation-and-induces-apoptosis-of-hepatic-stellate-cells-through-pi3k-akt-pathway
#16
Lili Zhu, Mingliang Cheng, Yongmei Liu, Yumei Yao, Zixin Zhu, Baofang Zhang, Qiuju Mou, Yiju Cheng
Liver fibrosis is a necessary stage for chronic liver diseases, and serious threat to human health. Hepatic fibrosis is a necessary stage for chronic liver diseases. Hepatic stellate cells (HSCs) are the primary cell type responsible for fibrosis. Thymosin beta 4 (Tβ4) has a potential role in the pathogenesis of liver fibrosis and that it is especially associated with the activation of HSCs, however, the underlying mechanisms are not fully elucidated. Herein, we investigated the potential role of Tβ4 in liver fibrosis by describing the effects of Tβ4, and we discuss the possible signaling pathway regulated by Tβ4...
June 28, 2017: Oncotarget
https://www.readbyqxmd.com/read/28694518/pdk1-plays-a-vital-role-on-hematopoietic-stem-cell-function
#17
Tianyuan Hu, Cong Li, Le Wang, Yingchi Zhang, Luyun Peng, Hui Cheng, Yajing Chu, Weili Wang, Hideo Ema, Yingdai Gao, Zhenyu Ju, Zhongzhou Yang, Xiaomin Wang, Tao Cheng, Weiping Yuan
3-Phosphoinositide-dependent protein kinase 1 (PDK1) is a pivotal regulator in the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway that have been shown to play key roles in the functional development of B and T cells via activation of AGC protein kinases during hematopoiesis. However, the role of PDK1 in HSCs has not been fully defined. Here we specifically deleted the PDK1 gene in the hematopoietic system and found that PDK1-deficient HSCs exhibited impaired function and defective lineage commitment abilities...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28694332/the-ets2-repressor-factor-erf-is-required-for-effective-primitive-and-definitive-hematopoiesis
#18
Ioanna Peraki, James Palis, George Mavrothalassitis
Erf is a ubiquitously expressed ets-DNA-binding containing transcriptional repressor. Erf haploinsufficiency causes craniosynostosis in human and mice, while its absence in mice leads to failed chorioallantoic fusion and death at E10.5. In this study, we show that Erf is required in all three waves of embryonic hematopoiesis. Mice lacking Erf in embryo proper exhibited severe anemia and died around embryonic day (E) 14.5. Erf epiblast specific knockout embryos had reduced numbers of circulating blood cells from E9...
July 10, 2017: Molecular and Cellular Biology
https://www.readbyqxmd.com/read/28692939/oligomeric-proanthocyanidin-derived-from-grape-seeds-inhibited-nf-%C3%AE%C2%BAb-signaling-in-activated-hsc-involvement-of-jnk-erk-mapk-and-pi3k-akt-pathways
#19
Min Jiang, Yan-Ling Wu, Xia Li, Yu Zhang, Kai-Li Xia, Ben-Wen Cui, Li-Hua Lian, Ji-Xing Nan
In current study, we aimed to reveal the potential antifibrotic effects of oligomeric proanthocyanidin (OPC) from grape seeds on lipopolysaccharide (LPS)-activated, HSC-T6, a rat hepatic stellate cell line. HSC-T6 cells were treated with OPC 1h prior to LPS, and then incubated for indicated time. OPC inhibited cells viability of HSC-T6 cells and decrease protein expression of collagen I, α-smooth muscle actin (α-SMA), tissue inhibitors of metalloproteinases I (TIMP-1) on LPS-induced HSC-T6 cells. OPC also significantly inhibited phosphorylation of LPS-stimulated phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt), extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK)...
July 7, 2017: Biomedicine & Pharmacotherapy, Biomédecine & Pharmacothérapie
https://www.readbyqxmd.com/read/28689803/lipopolysaccharides-induce-smad2-phosphorylation-through-pi3k-akt-and-mapk-cascades-in-hsc-t6-hepatic-stellate-cells
#20
Ying-Hsien Kao, Po-Han Chen, Tin-Ya Wu, Yu-Chun Lin, Ming-Shian Tsai, Po-Huang Lee, Tzong-Shyuan Tai, Huoy-Rou Chang, Cheuk-Kwan Sun
AIMS: Endotoxemia and its pro-fibrogenic signaling play a significant role in the development of hepatic fibrosis. This study investigated whether lipopolysaccharide (LPS) directly activate cultured HSC-T6 hepatic stellate cells (HSCs) through triggering Smad-dependent pro-fibrogenic signaling pathway. MAIN METHODS: Direct cell counting and assays for cell proliferation and migration were used to measure the effects of LPS on HSC behaviors. Quantitative PCR, Western blot, and gelatin zymography were used to quantify the molecular effects of LPS on expression of HSC activation markers and signaling activity...
July 6, 2017: Life Sciences
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