Hepatic Cell News Volume 1.45 | Dec 8 2017

TOP STORY

Measuring Mutation Accumulation in Single Human Adult Stem Cells by Whole-Genome Sequencing of Organoid Cultures

Researchers describe a protocol for human liver adult stem cells that can be completed over a period of 3–4 months with hands-on time of 5 days. [Nat Protoc] Abstract

(Ranked by impact factor of the journal)

Effect of Removing Kupffer Cells on Nanoparticle Tumor Delivery

Scientists hypothesized that the removal of the liver macrophages, cells that have been reported to take up the largest amount of circulating nanoparticles, would lead to a significant increase in the nanoparticle delivery efficiency to solid tumors. They were surprised to discover that the maximum achievable delivery efficiency was only 2%. [Proc Natl Acad Sci USA] Abstract

Adipocyte JAK2 Regulates Hepatic Insulin Sensitivity Independently of Body Composition, Liver Lipid Content, and Hepatic Insulin Signaling

Researchers determined the individual roles of hepatocyte and adipocyte Jak2 on whole body and tissue insulin sensitivity and liver metabolism. Concomitant deletion of Jak2 in hepatocytes and adipocytes completely normalized insulin sensitivity while reducing liver lipid content. [Diabetes] Abstract

Massive and Reproducible Production of Liver Buds Entirely from Human Pluripotent Stem Cells

Investigators identified three progenitor populations that can effectively generate liver buds in a highly reproducible manner: hepatic endoderm, endothelium, and septum mesenchyme. They achieved human scalability by developing an omni-well-array culture platform for mass producing homogeneous and miniaturized liver buds on a clinically relevant large scale. [Cell Rep] Full Article | Press Release | Graphical Abstract

Unacylated Ghrelin Prevents Mitochondrial Dysfunction in a Model of Ischemia/Reperfusion Liver Injury

The authors investigated the potential clinical impact of unacylated-ghrelin (UnAG) in a liver ischemia/reperfusion (I/R) rat model. They demonstrated that UnAG was able to reduce the lag-phase time in response to ADP administration and increase oxygen consumption in ex vivo experiments using liver mitochondria recovered from rats subjected to I/R. [Cell Death Dis] Full Article

Cell Penetrating Polymers Containing Guanidinium Trigger Apoptosis in Human Hepatocellular Carcinoma Cells Unless Conjugated to a Targeting N-Acetyl-Galactosamine Block

Researchers revealed that although guanidinium-based polymers have high membrane permeability, their application as plasmid delivery vehicles may be limited by their high cytotoxicity to certain cell types. [Bioconjug Chem] Abstract | Graphical Abstract

Mitochondrial Fission Promotes Cell Migration by Ca²⁺/CaMKII/ERK/FAK Pathway in Hepatocellular Carcinoma

The authors investigated the effect of mitochondrial fission on the migration and metastasis of hepatocellular carcinoma cells. [Liver Int] Abstract

Up-Regulation of Interleukin-21 Contributes to Liver Pathology of Schistosomiasis by Driving GC Immune Responses and Activating HSCs in Mice

Using a Schistosoma japonicum-infected mouse model, researchers studied the dynamics and effects of follicular helper T (Tfh) cells in vivo and demonstrated that Tfh phenotype molecules inducible costimulator, programmed death-1 and functional factor interleukin-21 were positively correlated with disease development by flow cytometry. [Sci Rep] Full Article

A Novel Y-Specific Long Non-Coding RNA Associated with Cellular Lipid Accumulation in HepG2 Cells and Atherosclerosis-Related Genes

Scientists found that lnc-KDM5D-4 was retained within the nucleus in hepatocytes. Its knockdown lead to changes in genes leading to increased lipid droplets formation in hepatocytes resulting in a downstream effect contributing to the chronic inflammatory process that underpin coronary artery disease. [Sci Rep] Full Article

Immortalization of Porcine 11β-Hydroxysteroid Dehydrogenase Type 1-Transgenic Liver Cells Using SV40 Large T Antigen

The SV40 large T antigen was transduced into primary 11β-hydroxysteroid dehydrogenase type 1 (HSD11B1)-transgenic (TG) hepatocytes, and those cells were immortalized. Immortalized HSD11B1-TG hepatocytes showed restored morphology, more rapid proliferation rate, and more expression of HSD11B1 than primary hepatocytes. [Int J Mol Sci] Full Article

ASPP2 Inhibits the Profibrotic Effects of Transforming Growth Factor-β1 in Hepatic Stellate Cells by Reducing Autophagy

The authors investigated the effects of apoptosis-stimulating protein of p53-2 (ASPP2) overexpression in hepatic stellate cells and the role of ASPP2 in mouse liver fibrogenesis. [Dig Dis Sci] Full Article

Human Hepatocyte Transplantation for Liver Disease: Current Status and Future Perspectives

Standardized techniques have been established for isolation, culture, and cryopreservation of human hepatocytes. Clinical hepatocyte transplantation safety and short-term efficacy have been proven; however, some major hurdles-mainly concerning shortage of donor organs, low cell engraftment, and lack of a long-lasting effect-need to be overcome to widen its clinical applications. [Pediatr Res] Abstract

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VALBIOTIS Announces Positive Preclinical Results for TOTUM-63, the Active Ingredient in VAL-63-NAFLD, for Non-Alcoholic Fatty Liver (NAFL), a Risk Factor for NASH

VALBIOTIS announced positive results for the active ingredient of VAL-63-NAFLD for NAFL, a risk factor for non-alcoholic steatohepatitis (NASH), and for the related metabolic parameters. [Press release from Valbiotis discussing research presented at the 2017 Congress of the International Diabetes Federation, Abu Dhabi] Press Release

Synlogic and Ginkgo Bioworks Announce Collaboration as First Step toward Building an Unprecedented Discovery Engine for Novel Living Medicines in Neurological and Liver Disorders

Ginkgo Bioworks, and Synlogic, Inc. announced a collaboration to discover new living medicines to treat neurological and liver disorders. [Synlogic, Inc.] Press Release

Madrigal’s MGL-3196 Achieves Primary Endpoint in Patients with Biopsy-Proven Non-Alcoholic Steatohepatitis (NASH) in Phase II Clinical Trial

Madrigal Pharmaceuticals, Inc. announced positive top-line results from a Phase II clinical trial in patients with biopsy-proven NASH. [Madrigal Pharmaceuticals, Inc.] Press Release

Investigation Finds Swedish Scientists Committed Scientific Misconduct

Two Swedish scientists have been found guilty of “misconduct in research” in a paper that they published in Science and later retracted. Their highly publicized work had suggested that tiny particles of plastic in the ocean harm fish. [Nature News] Editorial

US Graduate Students in Uproar over Proposed Tax Hike

Many US universities waive tuition for students who conduct research or teach. But a provision in a tax bill passed by the US House of Representatives would add that tuition to students’ taxable income. [Nature News] Editorial

Hundreds of German Universities Set to Lose Access to Elsevier Journals

Around 200 German universities will lose their subscriptions to Elsevier journals within weeks, because negotiations have failed to end a long-term contract dispute. [Nature News] Editorial

NEW Cold Spring Harbor (CSH): Mouse Development, Stem Cells & Cancer
June 6-25, 2018
Cold Spring Harbor, New York, United States

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NEW Postdoctoral Fellow – Liver Tissue Engineering (Massachusetts General Hospital and Harvard Medical School)

Research Associate – Non-Alcoholic Fatty Liver Disease (Newcastle University)

Assistant, Associate or Full Professor – Hepatology (University of California, San Diego)

Research Fellow – Hepatitis B Virology (National University of Singapore)

Research Scientist – Chronic Fibrotic and Metabolic Diseases (Gilead Sciences Inc.)

Postdoctoral Fellow – Liver-Like Organoids (KU Leuven)

Faculty Positions – Liver Health and Disease (University of Pittsburgh)

Postdoctoral Position – Liver Disease (University of Illinois)

Biomedical Scientist – Molecular and Cellular Gastroenterology (Mayo Clinic)

Faculty Position – Cancer Experimental Therapeutics (University of New Mexico)

Postdoctoral Research Fellow – Liver Tissue Engineering (Massachusetts General Hospital)

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