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Cholangiocyte hepatocyte

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https://www.readbyqxmd.com/read/28923495/crispr-cas9-engineering-of-adult-mouse-liver-demonstrates-that-the-dnajb1-prkaca-gene-fusion-is-sufficient-to-induce-tumors-resembling-fibrolamellar-hepatocellular-carcinoma
#1
Lars H Engelholm, Anjum Riaz, Denise Serra, Frederik Dagnæs-Hansen, Jens V Johansen, Eric Santoni-Rugiu, Steen H Hansen, Francesco Niola, Morten Frödin
BACKGROUND & AIMS: Fibrolamellar hepatocellular carcinoma (FL-HCC) is a primary liver cancer that predominantly affects young adults with no underlying liver disease. A somatic, 400 Kb deletion on chromosome 19 that fuses part of the DnaJ heat shock protein family (Hsp40) member B1 gene (DNAJB1) to the protein kinase cAMP-activated catalytic subunit alpha gene (PRKACA) has been repeatedly identified in patients with FL-HCC. However, the DNAJB1-PRKACA gene fusion has not been shown to induce liver tumorigenesis...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28903311/development-of-hepatoma-derived-bidirectional-oval-like-cells-as-a-model-to-study-host-interactions-with-hepatitis-c-virus-during-differentiation
#2
Masahiko Ito, Suofeng Sun, Takasuke Fukuhara, Ryosuke Suzuki, Miho Tamai, Toyohiko Yamauchi, Kenji Nakashima, Yoh-Ichi Tagawa, Shigetoshi Okazaki, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki
Directed differentiation of human stem cells including induced pluripotent stem cells into hepatic cells potentially leads to acquired susceptibility to hepatitis C virus (HCV) infection. However, cellular determinants that change their expression during cell reprogramming or hepatic differentiation and are pivotal for supporting the HCV life cycle remain unclear. In this study, by introducing a set of reprogramming factors, we established HuH-7-derived oval-like cell lines, Hdo-17 and -23, which possess features of bipotential liver precursors...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28878125/human-hepatic-organoids-for-the-analysis-of-human-genetic-diseases
#3
Yuan Guan, Dan Xu, Phillip M Garfin, Ursula Ehmer, Melissa Hurwitz, Greg Enns, Sara Michie, Manhong Wu, Ming Zheng, Toshihiko Nishimura, Julien Sage, Gary Peltz
We developed an in vitro model system where induced pluripotent stem cells (iPSCs) differentiate into 3-dimensional human hepatic organoids (HOs) through stages that resemble human liver during its embryonic development. The HOs consist of hepatocytes, and cholangiocytes, which are organized into epithelia that surround the lumina of bile duct-like structures. The organoids provide a potentially new model for liver regenerative processes, and were used to characterize the effect of different JAG1 mutations that cause: (a) Alagille syndrome (ALGS), a genetic disorder where NOTCH signaling pathway mutations impair bile duct formation, which has substantial variability in its associated clinical features; and (b) Tetralogy of Fallot (TOF), which is the most common form of a complex congenital heart disease, and is associated with several different heritable disorders...
September 7, 2017: JCI Insight
https://www.readbyqxmd.com/read/28853804/-benign-focal-liver-lesions-a-clinical-radiological-and-pathological-review
#4
Karim Abdelrahman, Sabine Schmidt, Amedeo Sciarra, Christine Sempoux
Benign focal liver lesions are a heterogeneous group of tumors of different cellular origin. They might develop from mesenchymal cells, hepatocytes or cholangiocytes. They are more often detected due to the increasing number of imaging investigations and the excellent performance of the new ultrasound machines. The imaging findings have to be interpreted while bearing the patient's clinical context in mind. The aim of this review is to discuss the three most frequent benign focal hepatic lesions : hemangioma, focal nodular hyperplasia and hepatocellular adenoma...
August 30, 2017: Revue Médicale Suisse
https://www.readbyqxmd.com/read/28834615/self-assembled-liver-organoids-recapitulate-hepato-biliary-organogenesis-in-vitro
#5
Dipen Vyas, Pedro M Baptista, Matthew Brovold, Emma Moran, Matthew Brovold, Brandon Gaston, Chris Booth, Michael Samuel, Anthony Atala, Shay Soker
Several 3D cell culture systems are currently available to create liver organoids. In general, these systems display better physiologic and metabolic aspects of intact liver tissue, compared with 2D culture systems. However, none of these reliably mimic human liver development, including parallel formation of hepatocyte and cholangiocyte anatomical structures. Here, we show that human fetal liver progenitor cells self-assemble inside acellular liver extracellular matrix (ECM) scaffolds to form 3D liver organoids that recapitulated several aspects of hepato-biliary organogenesis and resulted in concomitant formation of progressively more differentiated hepatocytes and bile duct structures...
August 23, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28833283/mir-337-3p-controls-hepatobiliary-gene-expression-and-transcriptional-dynamics-during-hepatic-cell-differentiation
#6
Céline Demarez, Claude Gérard, Sabine Cordi, Alexis Poncy, Younes Achouri, Nicolas Dauguet, David A Rosa, Patrick T Gunning, Isabelle Manfroid, Frédéric P Lemaigre
Transcriptional networks control the differentiation of the hepatocyte and cholangiocyte lineages from embryonic liver progenitor cells, and their subsequent maturation to the adult phenotype. However, how accurate levels of hepatocyte and cholangiocyte gene expression are determined during differentiation remains poorly understood. Here we identify miR-337-3p as a novel regulator of liver development. MiR-337-3p stimulates expression of cholangiocyte genes and represses hepatocyte genes in undifferentiated progenitor cells in vitro and in embryonic mouse livers...
August 17, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28794318/dysregulated-expression-of-mitf-in-subsets-of-hepatocellular-carcinoma-and-cholangiocarcinoma
#7
Nattakarn Nooron, Koji Ohba, Kazuhisa Takeda, Shigeki Shibahara, Anchalee Chiabchalard
Cholangiocarcinoma represents the second most common primary liver tumor after hepatocellular carcinoma. Mahanine, a carbazole alkaloid derived from Murraya koenigii (Linn.) Spreng, has been used as folk medicine in Thailand, where the liver fluke-associated cholangiocarcinoma is common. The expression of microphthalmia-associated transcription factor (MITF) is maintained at immunohistochemically undetectable levels in hepatocytes and cholangiocytes. To explore the regulation of MITF expression in the liver, we immunohistochemically analyzed the MITF expression using hepatocellular carcinoma and cholangiocarcinoma specimens of the human liver cancer tissue array...
August 2017: Tohoku Journal of Experimental Medicine
https://www.readbyqxmd.com/read/28777941/cholangiocytes-no-longer-cinderellas-to-the-hepatic-regenerative-response
#8
Malcolm R Alison
Biliary ductal cells proliferate from the portal areas of chronically damaged livers, but their significance to regeneration has been controversial. A recent article in Nature by Raven et al. (2017) now shows that blocking hepatocyte replication is essential for the hepatic differentiation of ductular cells after liver damage.
August 3, 2017: Cell Stem Cell
https://www.readbyqxmd.com/read/28777871/the-functional-characteristics-ccni-modulation-of-myeloid-derived-suppressor-cells-in-liver-inflammation
#9
Haiyan Zhang, Min Lian, Jun Zhang, Zhaolian Bian, Ruqi Tang, Qi Miao, Yanshen Peng, Jingyuan Fang, Zhengrui You, Pietro Invernizzi, Qixia Wang, M Eric Gershwin, Xiong Ma
There is increasing awareness of the immunologic roles of liver mononuclear populations including myeloid-derived suppressor cells (MDSCs). We took advantage of a large well defined cohort of 148 patients with liver inflammation and 45 health controls to focus on the qualitative and quantitative characteristics of MDSCs. We investigated the frequency, phenotype and functional capacities of MDSCs using peripheral blood MDSCs in a cohort of 55 patients with PBC, 40 with AIH, 39 with CHB, 14 with NAFLD and 45 healthy controls, and thereafter a liver targeted determination in 27 PBC, 27 AIH, 20 CHB, 14 NAFLD and 6 controls...
August 4, 2017: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/28765687/can-a-fibrotic-liver-afford-epithelial-mesenchymal-transition
#10
EDITORIAL
Stefan Munker, Yong-Le Wu, Hui-Guo Ding, Roman Liebe, Hong-Lei Weng
The question whether epithelial-mesenchymal transition (EMT) occurs during liver fibrogenesis is a controversial issue. In vitro studies confirm that hepatocytes or cholangiocytes undergo EMT upon transforming growth factor β (TGF-β) stimulation, whereas in vivo experiments based on genetic fate mapping of specific cell populations suggest that EMT does not occur in fibrotic animal models. In this review we present current data supporting or opposing EMT in chronic liver disease and discuss conditions for the occurrence of EMT in patients...
July 14, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28757171/genetic-determinants-of-cholangiopathies-molecular-and-systems-genetics
#11
REVIEW
Matthias C Reichert, Rabea A Hall, Marcin Krawczyk, Frank Lammert
Familial cholangiopathies are rare but potentially severe diseases. Their spectrum ranges from fairly benign conditions as, for example, benign recurrent intrahepatic cholestasis to low-phospholipid associated cholelithiasis and progressive familial intrahepatic cholestasis (PFIC). Many cholangiopathies such as primary biliary cholangitis (PBC) or primary sclerosing cholangitis (PSC) affect first the bile ducts ("ascending pathophysiology") but others, such as PFIC, start upstream in hepatocytes and cause progressive damage "descending" down the biliary tree and leading to end-stage liver disease...
July 27, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28754453/pathophysiologic-implications-of-innate-immunity-and-autoinflammation-in-the-biliary-epithelium
#12
REVIEW
Mario Strazzabosco, Romina Fiorotto, Massimiliano Cadamuro, Carlo Spirli, Valeria Mariotti, Eleanna Kaffe, Roberto Scirpo, Luca Fabris
The most studied physiological function of biliary epithelial cells (cholangiocytes) is to regulate bile flow and composition, in particular the hydration and alkalinity of the primary bile secreted by hepatocytes. After almost three decades of studies it is now become clear that cholangiocytes are also involved in epithelial innate immunity, in inflammation, and in the reparative processes in response to liver damage. An increasing number of evidence highlights the ability of cholangiocyte to undergo changes in phenotype and function in response to liver damage...
July 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28754450/pathogenesis-of-biliary-fibrosis
#13
REVIEW
Massimo Pinzani, Tu Vinh Luong
Chronic cholestatic liver diseases such as primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are associated with active hepatic fibrogenesis, and, ultimately, to the development of cirrhosis. However, the precise relationship between cholestasis, in its broad meaning, and liver tissue fibrosis is still poorly defined. Fibrogenesis is currently viewed as a dynamic process that appears strictly related to the extent and duration of parenchymal injury. This relationship is clearly evident in the presence of reiterative hepatocellular necrosis due to viral infection or alcohol abuse...
July 25, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28743983/liver-cholangiocytes-regenerate-hepatocytes-during-severe-liver-injury
#14
Iain Dickson
No abstract text is available yet for this article.
September 2017: Nature Reviews. Gastroenterology & Hepatology
https://www.readbyqxmd.com/read/28735098/cholangiocytes-cell-transplantation
#15
REVIEW
Lorenzo Ridola, Maria Consiglia Bragazzi, Vincenzo Cardinale, Guido Carpino, Eugenio Gaudio, Domenico Alvaro
BACKGROUND: Due to significant limitations to the access to orthotropic liver transplantation, cell therapies for liver diseases have gained large interest worldwide. SCOPE OF REVIEW: To revise current literature dealing with cell therapy for liver diseases. We discussed the advantages and pitfalls of the different cell sources tested so far in clinical trials and the rationale underlying the potential benefits of transplantation of human biliary tree stem cells (hBTSCs)...
July 19, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28729654/cryopreservation-protocol-for-human-biliary-tree-stem-progenitors-hepatic-and-pancreatic-precursors
#16
Lorenzo Nevi, Vincenzo Cardinale, Guido Carpino, Daniele Costantini, Sabina Di Matteo, Alfredo Cantafora, Fabio Melandro, Roberto Brunelli, Carlo Bastianelli, Camilla Aliberti, Marco Monti, Daniela Bosco, Pasquale Bartolomeo Berloco, Pierluigi Benedetti Panici, Lola Reid, Eugenio Gaudio, Domenico Alvaro
Human biliary tree stem/progenitor cells (hBTSCs) are being used for cell therapies of patients with liver cirrhosis. A cryopreservation method was established to optimize sourcing of hBTSCs for these clinical programs and that comprises serum-free Kubota's Medium (KM) supplemented with 10% dimethyl sulfoxide (DMSO), 15% human serum albumin (HSA) and 0.1% hyaluronans. Cryopreserved versus freshly isolated hBTSCs were similar in vitro with respect to self-replication, stemness traits, and multipotency. They were able to differentiate to functional hepatocytes,cholangiocytes or pancreatic islets, yielding similar levels of secretion of albumin or of glucose-inducible levels of insulin...
July 20, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28716722/dynamics-of-proliferative-and-quiescent-stem-cells-in-liver-homeostasis-and-injury
#17
Wanlu Cao, Kan Chen, Michiel Bolkestein, Yuebang Yin, Monique M A Verstegen, Marcel J C Bijvelds, Wenshi Wang, Nesrin Tuysuz, Derk Ten Berge, Dave Sprengers, Herold J Metselaar, Luc J W van der Laan, Jaap Kwekkeboom, Ron Smits, Maikel P Peppelenbosch, Qiuwei Pan
BACKGROUND & AIMS: Adult liver stem cells are usually maintained in a quiescent/slow-cycling state. However, a proliferative population, marked by leucine-rich repeat-containing G-protein coupled receptor 5 (LGR5), was recently identified as an important liver stem cell population. We aimed to investigate the dynamics and functions of proliferative and quiescent stem cells in healthy and injured livers. METHODS: We studied LGR5-positive stem cells using diphtheria toxin receptor and green fluorescent protein (GFP) knockin mice...
July 14, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28709961/bile-acids-fgf15-19-and-liver-regeneration-from-mechanisms-to-clinical-applications
#18
REVIEW
Gloria Alvarez-Sola, Iker Uriarte, Maria U Latasa, Maddalen Jimenez, Marina Barcena-Varela, Eva Santamaría, Raquel Urtasun, Carlos Rodriguez-Ortigosa, Jesús Prieto, Pedro Berraondo, Maite G Fernandez-Barrena, Carmen Berasain, Matías A Avila
The liver has an extraordinary regenerative capacity rapidly triggered upon injury or resection. This response is intrinsically adjusted in its initiation and termination, a property termed the "hepatostat". Several molecules have been involved in liver regeneration, and among them bile acids may play a central role. Intrahepatic levels of bile acids rapidly increase after resection. Through the activation of farnesoid X receptor (FXR), bile acids regulate their hepatic metabolism and also promote hepatocellular proliferation...
July 11, 2017: Biochimica et Biophysica Acta
https://www.readbyqxmd.com/read/28708602/development-of-hepatoma-derived-bidirectional-oval-like-cells-as-a-model-to-study-host-interactions-with-hepatitis-c-virus-during-differentiation
#19
Masahiko Ito, Suofeng Sun, Takasuke Fukuhara, Ryosuke Suzuki, Miho Tamai, Toyohiko Yamauchi, Kenji Nakashima, Yoh-Ichi Tagawa, Shigetoshi Okazaki, Yoshiharu Matsuura, Takaji Wakita, Tetsuro Suzuki
Directed differentiation of human stem cells including induced pluripotent stem cells into hepatic cells potentially leads to acquired susceptibility to hepatitis C virus (HCV) infection. However, cellular determinants that change their expression during cell reprogramming or hepatic differentiation and are pivotal for supporting the HCV life cycle remain unclear. In this study, by introducing a set of reprogramming factors, we established HuH-7-derived oval-like cell lines, Hdo-17 and -23, which possess features of bipotential liver precursors...
July 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28700576/cholangiocytes-act-as-facultative-liver-stem-cells-during-impaired-hepatocyte-regeneration
#20
Alexander Raven, Wei-Yu Lu, Tak Yung Man, Sofia Ferreira-Gonzalez, Eoghan O'Duibhir, Benjamin J Dwyer, John P Thomson, Richard R Meehan, Roman Bogorad, Victor Koteliansky, Yuri Kotelevtsev, Charles Ffrench-Constant, Luke Boulter, Stuart J Forbes
After liver injury, regeneration occurs through self-replication of hepatocytes. In severe liver injury, hepatocyte proliferation is impaired-a feature of human chronic liver disease. It is unclear whether other liver cell types can regenerate hepatocytes. Here we use two independent systems to impair hepatocyte proliferation during liver injury to evaluate the contribution of non-hepatocytes to parenchymal regeneration. First, loss of β1-integrin in hepatocytes with liver injury triggered a ductular reaction of cholangiocyte origin, with approximately 25% of hepatocytes being derived from a non-hepatocyte origin...
July 20, 2017: Nature
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