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https://www.readbyqxmd.com/read/28218626/building-discontinuous-liver-sinusoidal-vessels
#1
Courtney T Griffin, Siqi Gao
Blood vessels have a unified mission to circulate blood throughout the body; however, they have additional diverse and specialized roles in various organs. For example, in the liver, discontinuous sinusoids, which are fenestrated capillaries with intercellular gaps and a fragmented basement membrane, facilitate delivery of macromolecules to highly metabolic hepatocytes. During embryonic development, discontinuous sinusoids also allow circulating hematopoietic progenitor and stem cells to populate the liver and promote blood cell differentiation...
February 20, 2017: Journal of Clinical Investigation
https://www.readbyqxmd.com/read/28217369/regenerative-medicine-using-dental-pulp-stem-cells-for-liver-diseases
#2
EDITORIAL
Shogo Ohkoshi, Hajime Hara, Haruka Hirono, Kazuhiko Watanabe, Katsuhiko Hasegawa
Acute liver failure is a refractory disease and its prognosis, if not treated using liver transplantation, is extremely poor. It is a good candidate for regenerative medicine, where stem cell-based therapies play a central role. Mesenchymal stem cells (MSCs) are known to differentiate into multiple cell lineages including hepatocytes. Autologous cell transplant without any foreign gene induction is feasible using MSCs, thereby avoiding possible risks of tumorigenesis and immune rejection. Dental pulp also contains an MSC population that differentiates into hepatocytes...
February 6, 2017: World Journal of Gastrointestinal Pharmacology and Therapeutics
https://www.readbyqxmd.com/read/28215634/isolation-and-expansion-of-human-pluripotent-stem-cell-derived-hepatic-progenitor-cells-by-growth-factor-defined-serum-free-culture-conditions
#3
Takayuki Fukuda, Kazuo Takayama, Mitsuhi Hirata, Yu-Jung Liu, Kana Yanagihara, Mika Suga, Hiroyuki Mizuguchi, Miho K Furue
Limited growth potential, narrow ranges of sources, and difference in variability and functions from batch to batch of primary hepatocytes cause a problem for predicting drug-induced hepatotoxicity during drug development. Human pluripotent stem cell (hPSC)-derived hepatocyte-like cells in vitro are expected as a tool for predicting drug-induced hepatotoxicity. Several studies have already reported efficient methods for differentiating hPSCs into hepatocyte-like cells, however its differentiation process is time-consuming, labor-intensive, cost-intensive, and unstable...
February 16, 2017: Experimental Cell Research
https://www.readbyqxmd.com/read/28214206/involvement-of-prolyl-isomerase-pin1-in-the-cell-cycle-progression-and-proliferation-of-hepatic-oval-cells
#4
Prabodh Risal, Nirajan Shrestha, Lokendra Chand, Karl G Sylvester, Yeon Jun Jeong
Liver regenerates remarkably after toxic injury or surgical resection. In the case of failure of resident hepatocytes to restore loss, repopulation is carried out by induction, proliferation, and differentiation of the progenitor cell. Although, some signaling pathways have been verified to contribute oval cell-mediated liver regeneration, role of Peptidyl-prolyl cis-trans isomerase NIMA-interacting 1(Pin1) in the oval cells proliferation is unknown. In the present study, we evaluate the role of Pin1 in oval cells proliferation...
January 18, 2017: Pathology, Research and Practice
https://www.readbyqxmd.com/read/28213465/epithelial-morphogenesis-during-liver-development
#5
Naoki Tanimizu, Toshihiro Mitaka
Tissue stem/progenitor cells supply multiple types of epithelial cells that eventually acquire specialized functions during organ development. In addition, three-dimensional (3D) tissue structures need to be established for organs to perform their physiological functions. The liver contains two types of epithelial cells, namely, hepatocytes and cholangiocytes, which are derived from hepatoblasts, fetal liver stem/progenitor cells (LPCs), in mid-gestation. Hepatocytes performing many metabolic reactions form cord-like structures, whereas cholangiocytes, biliary epithelial cells, form tubular structures called intrahepatic bile ducts...
February 17, 2017: Cold Spring Harbor Perspectives in Biology
https://www.readbyqxmd.com/read/28210629/cellular-mechanisms-of-liver-regeneration-and-cell-based-therapies-of-liver-diseases
#6
REVIEW
Irina V Kholodenko, Konstantin N Yarygin
The emerging field of regenerative medicine offers innovative methods of cell therapy and tissue/organ engineering as a novel approach to liver disease treatment. The ultimate scientific foundation of both cell therapy of liver diseases and liver tissue and organ engineering is delivered by the in-depth studies of the cellular and molecular mechanisms of liver regeneration. The cellular mechanisms of the homeostatic and injury-induced liver regeneration are unique. Restoration of the mass of liver parenchyma is achieved by compensatory hypertrophy and hyperplasia of the differentiated parenchymal cells, hepatocytes, while expansion and differentiation of the resident stem/progenitor cells play a minor or negligible role...
2017: BioMed Research International
https://www.readbyqxmd.com/read/28209091/hgf-induced-dna-synthesis-in-hepatocytes-is-suppressed-by-p38
#7
Monica Aasrum, Ingvild J Brusevold, Thoralf Christoffersen, G Hege Thoresen
Previous studies in rat hepatocytes have shown that the MEK/ERK, PI3K/Akt and p38 pathways are all involved in the activation of DNA synthesis by EGF and that sustained activation of MEK/ERK is required. Here, we show that although HGF stimulated DNA synthesis and activated signaling in the same manner as EGF, the contribution of the signaling pathways to the induction of DNA synthesis differed. While HGF-induced DNA synthesis was dependent on MEK/ERK, with no significant contribution from PI3K/Akt, p38 suppressed HGF-induced DNA synthesis...
December 2016: Growth Factors
https://www.readbyqxmd.com/read/28199961/proteomic-analysis-of-laser-capture-microdissected-focal-lesions-in-a-rat-model-of-progenitor-marker-positive-hepatocellular-carcinoma
#8
Adeola O Adebayo Michael, Nagib Ahsan, Valerie Zabala, Heather Francois-Vaughan, Stephanie Post, Kate E Brilliant, Arthur R Salomon, Jennifer A Sanders, Philip A Gruppuso
We have shown previously that rapamycin, the canonical inhibitor of the mechanistic target of rapamycin (mTOR) complex 1, markedly inhibits the growth of focal lesions in the resistant hepatocyte (Solt-Farber) model of hepatocellular carcinoma (HCC) in the rat. In the present study, we characterized the proteome of persistent, pre-neoplastic focal lesions in this model. One group was administered rapamycin by subcutaneous pellet for 3 weeks following partial hepatectomy and euthanized 4 weeks after the cessation of rapamycin...
February 9, 2017: Oncotarget
https://www.readbyqxmd.com/read/28188341/evaluation-of-transcriptomic-signature-as-a-valuable-tool-to-study-drug-induced-cholestasis-in-primary-human-hepatocytes
#9
Céline Parmentier, Philippe Couttet, Armin Wolf, Thomas Zaccharias, Bruno Heyd, Philippe Bachellier, Marianne Uteng, Lysiane Richert
Primary human hepatocyte (PHH) sandwich cultures from five different donors were daily exposed to cyclosporine A (CsA), ibuprofen (IBU), chlorpromazine (CPZ), amiodarone (AMI) and paracetamol (APAP) at their respective Cmax (total) for short-term (1-3 days) and long-term treatment (14 days). Whole genome mRNA profiles (34,693 genes in total) were conducted using an Illumina microarray platform. The impact of compound treatments on gene signatures involved in liver differentiation, cholestasis and in bile acid homeostasis was evaluated...
February 10, 2017: Archives of Toxicology
https://www.readbyqxmd.com/read/28187190/widespread-gli-expression-but-limited-canonical-hedgehog-signaling-restricted-to-the-ductular-reaction-in-human-chronic-liver-disease
#10
Candice Alexandra Grzelak, Nicholas David Sigglekow, Janina Elke Eleonore Tirnitz-Parker, Elizabeth Jane Hamson, Alessandra Warren, Bharvi Maneck, Jinbiao Chen, Bramilla Patkunanathan, Jade Boland, Robert Cheng, Nicholas Adam Shackel, Devanshi Seth, David Geoffrey Bowen, Luciano Gastón Martelotto, D Neil Watkins, Geoffrey William McCaughan
Canonical Hedgehog (Hh) signaling in vertebrate cells occurs following Smoothened activation/translocation into the primary cilia (Pc), followed by a GLI transcriptional response. Nonetheless, GLI activation can occur independently of the canonical Hh pathway. Using a murine model of liver injury, we previously identified the importance of canonical Hh signaling within the Pc+ liver progenitor cell (LPC) population and noted that SMO-independent, GLI-mediated signals were important in multiple Pc-ve GLI2+ intrahepatic populations...
2017: PloS One
https://www.readbyqxmd.com/read/28170202/autologous-neohep-derived-from-chronic-hepatitis-b-virus-patients-blood-monocytes-by-upregulation-of-c-met-signaling
#11
Jashdeep Bhattacharjee, Barun Das, Disha Sharma, Preeti Sahay, Kshama Jain, Alaknanda Mishra, Srikanth Iyer, Puja Nagpal, Vinod Scaria, Perumal Nagarajan, Prakash Khanduri, Asok Mukhopadhyay, Pramod Upadhyay
In view of the escalating need for autologous cell-based therapy for treatment of liver diseases, a novel candidate has been explored in the present study. The monocytes isolated from hepatitis B surface antigen (HBsAg) nucleic acid test (NAT)-positive (HNP) blood were differentiated to hepatocyte-like cells (NeoHep) in vitro by a two-step culture procedure. The excess neutrophils present in HNP blood were removed before setting up the culture. In the first step of culture, apoptotic cells were depleted and genes involved in hypoxia were induced, which was followed by the upregulation of genes involved in the c-MET signaling pathway in the second step...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28170193/human-menstrual-blood-derived-stem-cells-ameliorate-liver-fibrosis-in-mice-by-targeting-hepatic-stellate-cells-via-paracrine-mediators
#12
Lijun Chen, Chunfeng Zhang, Lu Chen, Xiaojun Wang, Bingyu Xiang, Xiaoxing Wu, Yang Guo, Xiaozhou Mou, Li Yuan, Bo Chen, Jinfu Wang, Charlie Xiang
Mesenchymal stem cells (MSCs) may have potential applications in regenerative medicine for the treatment of chronic liver diseases (CLDs). Human menstrual blood is a novel source of MSCs, termed menstrual blood-derived stem cells (MenSCs). Compared with bone marrow MSCs, MenSCs exhibit a higher proliferation rate and they can be obtained through a simple, safe, painless procedure without ethical concerns. Although the therapeutic efficacy of MenSCs has been explored in some diseases, their effects on liver fibrosis are still unclear...
January 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28163185/genomic-characterization-and-dynamic-methylation-of-promoter-facilitates-transcriptional-regulation-of-h2a-variants-h2a-1-and-h2a-2-in-various-pathophysiological-states-of-hepatocyte
#13
Monica Tyagi, Divya Reddy, Sanjay Gupta
Differential expression of homomorphous variants of H2A family of histone H2A.1 and H2A.2 have been associated with hepatocellular carcinoma and maintenance of undifferentiated state of hepatocyte. However, not much is known about the transcriptional regulation of these H2A variants. The current study revealed the presence of 43bp 5'-regulatory region upstream of translation start site and a 26bp 3' stem loop conserved region for both the H2A.1 and H2A.2 variants. However, alignment of both H2A.1 and H2A.2 5'-untranslated region (UTR) sequences revealed no significant degree of homology between them despite the coding exon being very similar amongst the variants...
February 3, 2017: International Journal of Biochemistry & Cell Biology
https://www.readbyqxmd.com/read/28162154/-the-effect-of-semimature-dendritic-cell-and-the-levels-of-treg-on-transplantation-tolerance-of-hepatocytes-differentiated-from-mouse-embryonic-stem-cell
#14
C Zhang, W W Liao, B Cai, F R Liu, Q Ke, X F Zhu, X S He, A B Hu
Objective: To investigate the inducing effect and mechanism of semimature dendritic cell (smDCs) on transplantation tolerance of hepatocytes differentiated from mouse embryonic stem cells (ESCs), and to study the connections between smDCs and regulatory dendritic cells (regDCs). Methods: ESCs of 129 mouse labelled green fluorescent protein (GFP) were induced to hepatocytes by using previous methods. Meanwhile, bone marrow mononuclear cells of 129 mouse were induced to smDCs and regDCs. Moreover, the hepatocytes differentiated from 129 mouse ESCs were transplanted into liver of BALB/c mouse 3 days after infusing smDCs and regDCs suspension of 129 mouse into BALB/c mouse by tail vein respectively...
January 24, 2017: Zhonghua Yi Xue za Zhi [Chinese medical journal]
https://www.readbyqxmd.com/read/28157201/longitudinal-in-vivo-bioimaging-of-hepatocyte-transcription-factor-activity-following-cholestatic-liver-injury-in-mice
#15
Juliette M K M Delhove, Suzanne M K Buckley, Dany P Perocheau, Rajvinder Karda, Patrick Arbuthnot, Neil C Henderson, Simon N Waddington, Tristan R McKay
Molecular mechanisms regulating liver repair following cholestatic injury remain largely unknown. We have combined a mouse model of acute cholestatic liver injury, partial bile duct ligation (pBDL), with a novel longitudinal bioimaging methodology to quantify transcription factor activity during hepatic injury and repair. We administered lentiviral transcription factor activated luciferase/eGFP reporter (TFAR) cassettes to neonatal mice enabling longitudinal TFAR profiling by continued bioimaging throughout the lives of the animals and following pBDL in adulthood...
February 3, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28152052/choline-and-methionine-differentially-alter-methyl-carbon-metabolism-in-bovine-neonatal-hepatocytes
#16
Tawny L Chandler, Heather M White
Intersections in hepatic methyl group metabolism pathways highlights potential competition or compensation of methyl donors. The objective of this experiment was to examine the expression of genes related to methyl group transfer and lipid metabolism in response to increasing concentrations of choline chloride (CC) and DL-methionine (DLM) in primary neonatal hepatocytes that were or were not exposed to fatty acids (FA). Primary hepatocytes isolated from 4 neonatal Holstein calves were maintained as monolayer cultures for 24 h before treatment with CC (61, 128, 2028, and 4528 μmol/L) and DLM (16, 30, 100, 300 μmol/L), with or without a 1 mmol/L FA cocktail in a factorial arrangement...
2017: PloS One
https://www.readbyqxmd.com/read/28150711/generation-of-a-bile-salt-export-pump-deficiency-model-using-patient-specific-induced-pluripotent-stem-cell-derived-hepatocyte-like-cells
#17
Kazuo Imagawa, Kazuo Takayama, Shigemi Isoyama, Ken Tanikawa, Masato Shinkai, Kazuo Harada, Masashi Tachibana, Fuminori Sakurai, Emiko Noguchi, Kazumasa Hirata, Masayoshi Kage, Kenji Kawabata, Ryo Sumazaki, Hiroyuki Mizuguchi
Bile salt export pump (BSEP) plays an important role in hepatic secretion of bile acids and its deficiency results in severe cholestasis and liver failure. Mutation of the ABCB11 gene encoding BSEP induces BSEP deficiency and progressive familial intrahepatic cholestasis type 2 (PFIC2). Because liver transplantation remains standard treatment for PFIC2, the development of a novel therapeutic option is desired. However, a well reproducible model, which is essential for the new drug development for PFIC2, has not been established...
February 2, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28144825/a-transcriptomic-study-suggesting-human-ipsc-derived-hepatocytes-potentially-offer-a-better-in-vitro-model-of-hepatotoxicity-than-most-hepatoma-cell-lines
#18
Xiugong Gao, Yitong Liu
Hepatocytes derived from human induced pluripotent stem cells (iPSCs) hold great promise as an in vitro liver model by virtue of their unlimited long-term supply, stability and consistency in functionality, and affordability of donor diversity. However, the suitability of iPSC-derived hepatocytes (iPSC-Heps) for toxicology studies has not been fully validated. In the current study, we characterized global gene expression profiles of iPSC-Heps in comparison to those of primary human hepatocytes (PHHs) and several human hepatoma cell lines (HepaRG, HuH-7, HepG2, and HepG2/C3A)...
January 31, 2017: Cell Biology and Toxicology
https://www.readbyqxmd.com/read/28137721/transcriptional-functional-and-mechanistic-comparisons-of-stem-cell-derived-hepatocytes-heparg-cells-and-3d-human-hepatocyte-spheroids-as-predictive-in-vitro-systems-for-drug-induced-liver-injury
#19
Catherine C Bell, Volker M Lauschke, Sabine U Vorrink, Henrik Palmgren, Roger Duffin, Tommy B Andersson, Magnus Ingelman-Sundberg
Reliable and versatile hepatic in vitro systems for the prediction of drug pharmacokinetics and toxicity are essential constituents of preclinical safety assessment pipelines for new medicines. Here, we compared three emerging cell systems, hepatocytes derived from induced pluripotent stem cells (hiPS-Hep), HepaRG cells and 3D primary human hepatocyte (PHH) spheroids at transcriptional and functional levels in a multi-center study to evaluate their potential as predictive models for drug-induced hepatotoxicity...
January 30, 2017: Drug Metabolism and Disposition: the Biological Fate of Chemicals
https://www.readbyqxmd.com/read/28132119/epa-dha-and-lipoic-acid-differentially-modulate-the-n-3-fatty-acid-biosynthetic-pathway-in-atlantic-salmon-hepatocytes
#20
Marta Bou, Tone-Kari Østbye, Gerd M Berge, Bente Ruyter
The aim of the present study was to investigate how EPA, DHA, and lipoic acid (LA) influence the different metabolic steps in the n-3 fatty acid (FA) biosynthetic pathway in hepatocytes from Atlantic salmon fed four dietary levels (0, 0.5, 1.0 and 2.0%) of EPA, DHA or a 1:1 mixture of these FA. The hepatocytes were incubated with [1-(14)C] 18:3n-3 in the presence or absence of LA (0.2 mM). Increased endogenous levels of EPA and/or DHA and LA exposure both led to similar responses in cells with reduced desaturation and elongation of [1-(14)C] 18:3n-3 to 18:4n-3, 20:4n-3, and EPA, in agreement with reduced expression of the Δ6 desaturase gene involved in the first step of conversion...
January 28, 2017: Lipids
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