Hepatic Cell News Volume 1.07 | Mar 10 2017

TOP STORY

Bone Marrow Stem Cell Therapy Partially Ameliorates Pathological Consequences in Livers of Mice Expressing Mutant Human α1-Antitrypsin

Hepatocytes are the primary affected cells in alpha-1-antitrypsin (AAT) deficiency (AATD), scientists investigated whether transplantation of bone marrow (BM)-derived stem cells in transgenic mice expressing human AATZ (the Z variant of AAT) confers any competitive advantages compared to host cells that could lead to pathological improvement. Transplantation of cells resulted in the decline of globule-containing hepatocytes, improvement in proliferation of globule-devoid hepatocytes from the host-derived hepatocytes, and apparently, donor-derived cells. [Hepatology] Abstract

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Ablation of Cytochrome P450 Omega-Hydroxylase 4A14 Gene Attenuates Hepatic Steatosis and Fibrosis

The authors aimed to determine the role of cytochrome P450 omega-hydroxylase 4A14 (CYP4A14) in the development and the progression of nonalcoholic fatty liver disease (NAFLD). They showed that hepatic CYP4A expression was up-regulated in the livers of patients and three murine models of NAFLD. [Proc Natl Acad Sci USA] Abstract

An FGFR Inhibitor Converts the Tumor Promoting Effect of TGF-β by the Induction of Fibroblast-Associated Genes of Hepatoma Cells

Researchers showed TGF-β1 combined with AZD4547, a fibroblast growth factors receptor (FGFR) inhibitor, transformed hepatoma cells into less malignant fibroblast-like cells with respect to morphology, physiological properties, and gene expression profiles. [Oncogene] Abstract

Generation of Human Liver Chimeric Mice with Hepatocytes from Familial Hypercholesterolemia Induced Pluripotent Stem Cells

The authors engrafted familial hypercholesterolemia differentiated hepatocytes into the liver of Ldlr^−/−/Rag2^−/−/Il2rg^−/− mice, and assessed the effect of these same medications on low-density lipoprotein cholesterol clearance and endothelium-dependent vasodilation in vivo. [Stem Cell Reports] Full Article | Graphical Abstract

Paracrine Signals Regulate Human Liver Organoid Maturation from iPSC

Scientists showed mesoderm-derived paracrine signals promote hepatocyte maturation in liver organoids, but organoid self-organization requires cell-to-cell surface contact. Their in vitro model demonstrated a novel approach to identify developmental paracrine signals regulating the differentiation of human hepatocytes. [Development] Full Article

Development of Liver Decellularized Extracellular Matrix Bioink for 3D Cell Printing-Based Liver Tissue Engineering

Researchers developed a liver decellularized extracellular matrix (dECM) bioink for three-dimensional (3D) cell printing applications and evaluated its characteristics. Stem cell differentiation and HepG2 cell functions in the liver dECM bioink in comparison to commercial collagen bioink were evaluated, and the liver dECM bioink was found to induce stem cell differentiation and enhance HepG2 cell function. [Biomacromolecules] Abstract

Amigo2-Upregulation in Tumor Cells Facilitates their Attachment to Liver Endothelial Cells Resulting in Liver Metastases

Investigators found that amphoterin-induced gene and open reading frame 2 (amigo2) expression in human cancers was higher in liver metastatic lesions than in primary lesions. Amigo2 regulated tumor cell adhesion to liver endothelial cells and formation of liver metastases. [Sci Rep] Full Article

Inhibiting Histone Deacetylases Suppresses Glucose Metabolism and Hepatocellular Carcinoma Growth by Restoring FBP1 Expression

The authors demonstrated that expression of fructose-1,6-bisphosphatase (FBP1) was downregulated in hepatocellular carcinoma (HCC) patient specimens and decreased expression of FBP1 associated with poor prognosis. Low expression of FBP1 correlated with high levels of histone deacetylase 1 (HDAC1) and HDAC2 proteins in HCC patient tissues. [Sci Rep] Full Article

Sulfasalazine Attenuates Evading Anticancer Response of CD133-Positive Hepatocellular Carcinoma Cells

Researchers found that oxidative stress increase CD133 expression in hepatocellular carcinoma (HCC) and increased CD133 expression enhanced the capacity of the defense system against ROS, and thereby play a central role in resistance to liver cancer therapy. Moreover, ablation of CD133 attenuated not only the capacity for defense against ROS, but also chemoresistance, in HCC through decreasing glutathione levels in vitro. [J Exp Clin Cancer Res] Full Article

TRAF4 Regulates Migration, Invasion and the Epithelial-Mesenchymal Transition via PI3K/AKT Signaling in Hepatocellular Carcinoma

Scientists found that tumor necrosis factor receptor-associated factor 4 (TRAF4) was highly expressed in hepatocellular carcinoma (HCC) cell lines and HCC tissues compared with normal liver cell line and adjacent noncancerous tissue. TRAF4 overexpression in HCC tissues was correlated with tumor numbers and vascular invasion. [Oncol Res] Full Article

Toyocamycin Attenuates Free Fatty Acid-Induced Hepatic Steatosis and Apoptosis in Cultured Hepatocytes and Ameliorates Nonalcoholic Fatty Liver Disease in Mice

Investigators examined the effect of toyocamycin on hepatocyte lipoapoptosis and steatosis. They also explored the effects of toyocamycin in a mouse model of nonalcoholic fatty liver disease. [PLoS One] Full Article

Hepatostat: Liver Regeneration and Normal Liver Tissue Maintenance

The author discusses the complex mechanisms involved in maintaining liver size homeostasis uniquely hepatic process encompass a variety of regenerative pathways that are specific to different types of injury. [Hepatology] Abstract

Targeting Hepatic Macrophages to Treat Liver Diseases

The author discusses pathogenic macrophage subsets that can be successfully translated into novel treatment options for patients with liver diseases. [J Hepatol] Abstract | Graphical Abstract

Visit our reviews page to see a complete list of reviews in the hepatic cell research field.

Grant Awarded to Sanford Simon Will Fund Research to Treat Rare Liver Cancer

Dr. Sanford Simon, head of the Laboratory of Cellular Biophysics at Rockefeller University, has been awarded a $600,000 grant by the Fibrolamellar Cancer Foundation to develop a therapy for fibrolamellar hepatocellular carcinoma. [Rockefeller University] Press Release

Exelixis’ Cabozantinib Granted Orphan Drug Designation for the Treatment of Hepatocellular Carcinoma

Exelixis, Inc. announced that the U.S. Food & Drug Administration has granted orphan drug designation to cabozantinib for the treatment of hepatocellular carcinoma. [Exelixis, Inc.] Press Release

Alnylam Receives European Medicines Agency PRIME Designation for Accelerated Assessment of Givosiran, an Investigational RNAi Therapeutic for the Treatment of Acute Hepatic Porphyrias

Alnylam Pharmaceuticals, Inc. announced that the European Medicines Agency has granted access to its Priority Medicines scheme for givosiran, an investigational RNAi therapeutic targeting aminolevulinic acid synthase 1 for the treatment of acute hepatic porphyrias. [Alnylam Pharmaceuticals, Inc.] Press Release

Patchy Progress on Fixing Global Gender Disparities in Science

Although women are publishing more studies, being cited more often, and securing more coveted first-author positions than they were in the mid 1990s, overall progress towards gender parity in science varies widely by country and field. This is according to a massive report released on 8^th March that is the first to examine such a broad swath of disciplines and regions of the world over time. [Nature News] Editorial

Open-Data Contest Unearths Scientific Gems — and Controversy

When a prestigious medical journal challenged scientists to analyze data from a pivotal blood-pressure study in search of new findings, hundreds of researchers around the world rushed to sign up. The contest, sponsored by the New England Journal of Medicine, offered scientists a rare opportunity to access detailed trial data that otherwise might have remained proprietary for another year — if not indefinitely. But the competition, whose winners were announced on 7^th March, also illustrates the tension between speeding access to data and protecting the interests of those who labored to collect them. [Nature News] Editorial

NEW Metabolism in Time and Space: Emerging Links to Cellular and Developmental Programs
May 11-13, 2017
Heidelberg, Germany

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NEW Postdoctoral Fellowship – Metabolism (University of San Francisco)

Research Fellow – Hepatocytes (National University of Singapore)

Academic Pathologist – Liver/GI (University of Texas Southwestern Medical Center)

Associate or Full Professor – Gastroenterology (University of Washington)

Postdoctoral Fellow – Non-Alcoholic Steatohepatitis (AstraZeneca)

Postdoctoral Position – Liver Fibrosis (Massachusetts General Hospital)

Postdoctoral Fellow – Non-Alcoholic Fatty Liver Disease (University of Gothenburg)

PhD Studentship – Hepatocytes (KU Leuven, Stem Cell Institute)

Senior Scientist – Oncology (Genentech Research)

Training Fellowship – Clinical Research (University of Oxford)

Postdoctoral Associate – Cancer Biology (University of Florida)

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