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Hepatic microenvironment

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https://www.readbyqxmd.com/read/29758331/liver-regeneration-requires-yap1-tgf%C3%AE-dependent-epithelial-mesenchymal-transition-in-hepatocytes
#1
Seh-Hoon Oh, Marzena Swiderska-Syn, Mark L Jewell, Richard T Premont, Anna Mae Diehl
BACKGROUND: Chronic failure of mechanisms that promote effective regeneration of dead hepatocytes causes replacement of functional hepatic parenchyma with fibrous scar and ultimately results in cirrhosis. Therefore, defining and optimizing mechanisms that orchestrate effective regeneration might prevent cirrhosis. We hypothesized that effective regeneration of injured livers requires hepatocytes to evade the growth inhibitory actions of TGF-β since TGF-β signaling inhibits mature hepatocyte growth but drives cirrhosis pathogenesis...
May 11, 2018: Journal of Hepatology
https://www.readbyqxmd.com/read/29750997/the-role-of-spatial-variations-of-abiotic-factors-in-mediating-intratumour-phenotypic-heterogeneity
#2
Tommaso Lorenzi, Chandrasekhar Venkataraman, Alexander Lorz, Mark A J Chaplain
We present here a space- and phenotype-structured model of selection dynamics between cancer cells within a solid tumour. In the framework of this model, we combine formal analyses with numerical simulations to investigate in silico the role played by the spatial distribution of abiotic components of the tumour microenvironment in mediating phenotypic selection of cancer cells. Numerical simulations are performed both on the 3D geometry of an in silico multicellular tumour spheroid and on the 3D geometry of an in vivo human hepatic tumour, which was imaged using computerised tomography...
May 8, 2018: Journal of Theoretical Biology
https://www.readbyqxmd.com/read/29704254/intrahepatic-t-cell-receptor-%C3%AE-immune-repertoire-is-essential-for-liver-regeneration
#3
Qing Liang, Zeyuan Liu, Chao Zhu, Bin Wang, Xiaoke Liu, Yanan Yang, Xue Lv, Haiyu Mu, Kejia Wang
T lymphocytes synergize with the cellular immune system to promote hepatocyte regeneration. The T cell receptor (TCR) immune repertoire is closely associated with the host immune response and regenerative proliferation. High-throughput sequencing of TCR provides deep insight into monitoring the immune microenvironment. Here, we aimed to determine the role of the TCRβ immune repertoire in liver regeneration. We investigated the hepatic regeneration in TCRβ chain-deficient (Tcrb-/- ) mice by two-thirds partial hepatectomy (PHx) method...
April 27, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29703082/fabrication-of-a-co-culture-micro-bioreactor-device-for-efficient-hepatic-differentiation-of-human-induced-pluripotent-stem-cells-hipscs
#4
Mousa Kehtari, Bahman Zeynali, Masoud Soleimani, Mahboubeh Kabiri, Ehsan Seyedjafari
Primary hepatocytes, as the gold standard cell type for in vitro models, lose their characteristic morphology and functions after few days. There is an urgent need to develop physiologically relevant models that recapitulate liver microenvironment to obtain mature hepatocyte from stem cells. We designed and fabricated a micro-bioreactor device mimicking the physiological shear stress and cell-cell interaction in liver sinusoid microenvironment. Induced pluripotent stem cells (iPSCs) were co-cultured with human umbilical vein endothelial cells (HUVECs) in the micro-bioreactor device with continuous perfusion of hepatic differentiation medium (100 μL/h)...
April 27, 2018: Artificial Cells, Nanomedicine, and Biotechnology
https://www.readbyqxmd.com/read/29695839/repression-of-let-7a-cluster-prevents-adhesion-of-colorectal-cancer-cells-by-enforcing-a-mesenchymal-phenotype-in-presence-of-liver-inflammation
#5
Lipeng Cheng, Li Geng, Binghua Dai, Tao Zheng, Jun Fu, Liang Qiao, Wenchang Cai, Yue Wang, Jiamei Yang
The liver is the most common site of metastasis in patients with colorectal cancer, and colorectal cancer liver metastasis (CRLM) is associated with poor rates of survival. However, CRLM occurs infrequently in livers exhibiting signs of hepatitis or cirrhosis, suggesting a role for inflammation in attenuating CRLM. The molecular mechanisms driving this phenomenon remain unclear. The aim of this study was to confirm the mechanism by which liver inflammation inhibits CRLM. We used BALB/c animal models of inflammatory liver diseases to confirm that liver inflammation inhibits CRLM, and then elucidated the molecular mechanisms governing that process...
April 25, 2018: Cell Death & Disease
https://www.readbyqxmd.com/read/29689279/hepatitis-b-virus-x-protein-elevates-parkin-mediated-mitophagy-through-lon-peptidase-in-starvation
#6
Xiao-Yun Huang, Dan Li, Zhi-Xin Chen, Yue-Hong Huang, Wen-Yu Gao, Bi-Yun Zheng, Xiao-Zhong Wang
Hepatocellular Carcinoma (HCC) is the fifth most prevalent cancer worldwide. Specially, Hepatitis B viurs X protein (HBx) is a leading factor in the progression of Hepatitis B viurs-related HCC. Nutrient-deprived tumor microenvironment also contributes to tumor development. However, the role of HBx in nutrient-deprived HCC has received little investigation. Here, we show that HBx elevates PINK1-Parkin mediating mitophagy in starvation. HBx not only increases the PINK1/Parkin gene expression but also accelerates Parkin recruitment to partial mitochondria...
April 21, 2018: Experimental Cell Research
https://www.readbyqxmd.com/read/29678444/biliary-epithelium-a-neuroendocrine-compartment-in-cholestatic-liver-disease
#7
REVIEW
Laurent Ehrlich, Marinda Scrushy, Fanyin Meng, Terry C Lairmore, Gianfranco Alpini, Shannon Glaser
Hepatic fibrosis is characterized by abnormal accumulation of extracellular matrix (ECM) that can lead to ductopenia, cirrhosis, and even malignant transformation. In this review, we examine cholestatic liver diseases characterized by extensive biliary fibrosis such as primary sclerosing cholangitis (PSC), primary biliary cholangitis (PBC), polycystic liver disease (PLD), and MDR2-/- and BDL mouse models. Following biliary injury, cholangiocytes, the epithelial cells that line the bile ducts, become reactive and adopt a neuroendocrine phenotype in which they secrete and respond to neurohormones and neuropeptides in an autocrine and paracrine fashion...
April 17, 2018: Clinics and Research in Hepatology and Gastroenterology
https://www.readbyqxmd.com/read/29675734/co-culture-system-of-hepatocytes-and-endothelial-cells-two-in-vitro-approaches-for-enhancing-liver-specific-functions-of-hepatocytes
#8
Gaoxiong Wang, Youshi Zheng, Yingchao Wang, Zhixiong Cai, Naishun Liao, Jingfeng Liu, Wenmin Zhang
Although hepatocyte transplantation and bioartificial liver support system provide new promising opportunities for those patients waiting for liver transplantation, hepatocytes are easily losing liver-specific functions by using the common in vitro cultured methods. The co-culture strategies with mimicking the in vivo microenvironment would facilitate the maintenance of liver-specific functions of hepatocytes. Considering that hepatocytes and endothelial cells (ECs) account for 80-90% of total cell populations in the liver, hepatocytes and ECs were directly co-cultured with hepatic stellate cells (HSCs) or adipose tissue-derived stem cells (ADSCs) at a ratio of 700:150:3 or 14:3:3 in the present study, and the liver-specific functions were carefully analyzed...
April 19, 2018: Cytotechnology
https://www.readbyqxmd.com/read/29644002/loss-of-neutrophil-polarization-in-colon-carcinoma-liver-metastases-of-mice-with-an-inducible-liver-specific-igf-i-deficiency
#9
Roni F Rayes, Simon Milette, Maria Celia Fernandez, Boram Ham, Ni Wang, France Bourdeau, Stephanie Perrino, Shoshana Yakar, Pnina Brodt
The growth of cancer metastases in the liver depends on a permissive interaction with the hepatic microenvironment and neutrophils can contribute to this interaction, either positively or negatively, depending on their phenotype. Here we investigated the role of IGF-I in the control of the tumor microenvironment in the liver, using mice with a conditional, liver-specific, IGF-I deficiency (iLID) induced by a single tamoxifen injection. In mice that had a sustained (3 weeks) IGF-I deficiency prior to the intrasplenic/portal inoculation of colon carcinoma MC-38 cells, we observed an increase in neutrophil accumulation in the liver relative to controls...
March 20, 2018: Oncotarget
https://www.readbyqxmd.com/read/29643975/physiological-hypoxia-enhances-stemness-preservation-proliferation-and-bidifferentiation-of-induced-hepatic-stem-cells
#10
Xiaosong Zhi, Jun Xiong, Mengchao Wang, Hongxia Zhang, Gang Huang, Jian Zhao, Xiaoyuan Zi, Yi-Ping Hu
Induced hepatic stem cells (iHepSCs) have great potential as donors for liver cell therapy due to their self-renewal and bipotential differentiation properties. However, the efficiency of bidifferentiation and repopulation efficiency of iHepSCs is relatively low. Recent evidence shows that physiological hypoxia, a vital factor within stem cell "niche" microenvironment, plays key roles in regulating tissue stem cell biological behaviors including proliferation and differentiation. In this study, we found that physiological hypoxia (10% O2 ) enhanced the stemness properties and promoted the proliferation ability of iHepSCs by accelerating G1/S transition via p53-p21 signaling pathway...
2018: Oxidative Medicine and Cellular Longevity
https://www.readbyqxmd.com/read/29643856/the-contribution-of-non-professional-antigen-presenting-cells-to-immunity-and-tolerance-in-the-liver
#11
REVIEW
Christina Mehrfeld, Steven Zenner, Miroslaw Kornek, Veronika Lukacs-Kornek
The liver represents a unique organ biased toward a tolerogenic milieu. Due to its anatomical location, it is constantly exposed to microbial and food-derived antigens from the gut and thus equipped with a complex cellular network that ensures dampening T-cell responses. Within this cellular network, parenchymal cells (hepatocytes), non-parenchymal cells (liver sinusoidal endothelial cells and hepatic stellate cells), and immune cells contribute directly or indirectly to this process. Despite this refractory bias, the liver is capable of mounting efficient T-cell responses...
2018: Frontiers in Immunology
https://www.readbyqxmd.com/read/29627914/the-influence-of-feed-supplementation-with-probiotic-strain-lactobacillus-reuteri-ccm-8617-and-alginite-on-intestinal-microenvironment-of-spf-mice-infected-with-salmonella-typhimurium-ccm-7205
#12
Soňa Gancarčíková, Radomíra Nemcová, Miroslav Popper, Gabriela Hrčková, Ľuboslava Sciranková, Marián Maďar, Dagmar Mudroňová, Štefan Vilček, Rudolf Žitňan
Alginite is a non-ore raw material arising by fossilization of accumulated organic (algae) and inorganic material, particularly clay, carbonates, quartz, and amorphous modification of silicic acid in the aqueous environment. Humic acids as a component of organic portion of alginite are known for very good buffering ability which allows them to stabilise pH throughout the digestion system of animals, stimulate receptors of the immune system in intestinal villi against pathogenic bacteria, and support proliferation and activity of beneficial bacteria (lactobacilli, bifidobacteria, and similar)...
April 7, 2018: Probiotics and Antimicrobial Proteins
https://www.readbyqxmd.com/read/29621784/exosomes-derived-from-dendritic-cells-attenuate-liver-injury-by-modulating-the-balance-of-treg-and-th17-cells-after-ischemia-reperfusion
#13
Lei Zheng, Zhi Li, Wei Ling, Deming Zhu, Zhiwen Feng, Lianbao Kong
BACKGROUND/AIMS: The present study aimed to evaluate the effects as well as the underlying mechanisms of bone marrow-derived dendritic cells (BMDCs) and exosomes produced by BMDCs (DEXs) on hepatic ischemia-reperfusion (I/R) injury (IRI). METHODS: Primary hepatocytes were isolated and used to mimic the liver IR microenvironment. BMDCs were induced and characterized both biochemically with a flow cytometer (FCM) and biophysically with a microscope. Then, we exposed BMDCs to the supernatants from primary hepatocytes and evaluated the maturation of BMDCs by FCM...
March 29, 2018: Cellular Physiology and Biochemistry
https://www.readbyqxmd.com/read/29619366/targeting-endoplasmic-reticulum-and-or-mitochondrial-ca-2-fluxes-as-therapeutic-strategy-for-hcv-infection
#14
Rosella Scrima, Claudia Piccoli, Darius Moradpour, Nazzareno Capitanio
Chronic hepatitis C is characterized by metabolic disorders and by a microenvironment in the liver dominated by oxidative stress, inflammation and regeneration processes that can in the long term lead to liver cirrhosis and hepatocellular carcinoma. Several lines of evidence suggest that mitochondrial dysfunctions play a central role in these processes. However, how these dysfunctions are induced by the virus and whether they play a role in disease progression and neoplastic transformation remains to be determined...
2018: Frontiers in Chemistry
https://www.readbyqxmd.com/read/29616383/progression-of-conventional-hepatic-cell-culture-models-to-bioengineered-hepg2-cells-for-evaluation-of-herbal-bioactivities
#15
REVIEW
Pardeep Kaur, Robin, Rajendra G Mehta, Saroj Arora, Balbir Singh
Cancer cell lines of human tissue origin have been extensively used to investigate antiproliferative activity and toxicity of herbal extracts, isolated compounds, and anticancer drugs. These cell lines are genetically and/or epigenetically well characterized to determine the altered expression of proteins within given cellular pathways and critical genes in cancer. Human derived hepatoma (HepG2) cell line has been extensively exploited to examine cytoprotective, antioxidative, hepatoprotective, anti-hepatoma, hypocholesterolemic, anti-steatosis, bioenergetic homeostatic and anti-insulin resistant properties...
April 3, 2018: Biotechnology Letters
https://www.readbyqxmd.com/read/29607608/three-dimensional-co-culture-of-primary-hepatocytes-and-stellate-cells-in-silk-scaffold-improves-hepatic-morphology-and-functionality-in-vitro
#16
Guofeng Wei, Jiwen Wang, Qiang Lv, Ming Liu, Hong Xu, He Zhang, Lingling Jin, Jiachuan Yu, Xiuli Wang
A vigorous in vitro model of liver that could recapitulate hepatic phenotype and functionality in vivo would exclusively improve the efficiency of bioartificial liver, drug discovery or even transplantation therapy. Owing to the indispensable role of 3D microenvironment in supporting viability and function of hepatocytes in vitro, much effort recently has been focused on improving reproducibility and standardization of primary hepatocyte cultures with a paradigm shift to 3D culture system, In the present study, an improved 3D co-culture system of hepatocytes was established in which rat primary hepatocytes were co-cultured with hepatic stellate cells in silk porous scaffolds...
April 1, 2018: Journal of Biomedical Materials Research. Part A
https://www.readbyqxmd.com/read/29604220/liver-angiopoietin-2-is-a-key-predictor-of-de-novo-or-recurrent-hepatocellular-cancer-after-hcv-direct-acting-antivirals
#17
Francesca Faillaci, Luca Marzi, Rosina Critelli, Fabiola Milosa, Filippo Schepis, Elena Turola, Silvia Andreani, Gabriele Vandelli, Veronica Bernabucci, Barbara Lei, Federica D'Ambrosio, Laura Bristot, Luisa Cavalletto, Liliana Chemello, Pamela Sighinolfi, Paola Manni, Antonino Maiorana, Cristian Caporali, Marcello Bianchini, Maria Marsico, Laura Turco, Nicola de Maria, Mariagrazia Del Buono, Paola Todesca, Luca di Lena, Dante Romagnoli, Paolo Magistri, Fabrizio di Benedetto, Savino Bruno, Gloria Taliani, Gianluigi Giannelli, Maria-Luz Martinez-Chantar, Erica Villa
Recent reports suggested that direct acting antivirals (DAAs) might favor hepatocellular carcinoma (HCC).In Study 1,we studied the proangiogenic liver microenvironment in 242 DAAs-treated chronic Hepatitis C patients with advanced fibrosis.Angiopoietin-2 expression was studied in tissue (cirrhotic and/or neoplastic) from recurrent,de novo,non-recurrent HCC or patients never developing HCC.Circulating Angiopoietin-2,vascular-endothelial growth factor (VEGF),and C-reactive protein were also measured. In Study 2,we searched for factors associated with de novo HCC in 257 patients with cirrhosis of different etiologies enrolled in a dedicated prospective study...
March 31, 2018: Hepatology: Official Journal of the American Association for the Study of Liver Diseases
https://www.readbyqxmd.com/read/29593314/oncofetal-gene-sall4-reactivation-by-hepatitis-b-virus-counteracts-mir-200c-in-pd-l1-induced-t-cell-exhaustion
#18
Cheng Sun, Peixiang Lan, Qiuju Han, Mei Huang, Zhihong Zhang, Geliang Xu, Jiaxi Song, Jinyu Wang, Haiming Wei, Jian Zhang, Rui Sun, Cai Zhang, Zhigang Tian
A chronic viral or tumor microenvironment can push T cells to exhaustion by promoting coinhibitory ligand expression. However, how host factors control coinhibitory ligand expression and whether viral infection breaks this control during tumor progress is unknown. Here we show a close negative correlation between SALL4 or PD-L1 and miR-200c in tumors from 98 patients with HBV-related hepatocellular carcinoma. SALL4 or PD-L1 expression correlates negatively with miR-200c expression, and patients with lower levels of SALL4 or PD-L1 and higher miR-200c survive longer...
March 28, 2018: Nature Communications
https://www.readbyqxmd.com/read/29572702/depleted-polymorphonuclear-leukocytes-in-human-metastatic-liver-reflect-an-altered-immune-microenvironment-associated-with-recurrent-metastasis
#19
Fiona Hand, Cathal Harmon, Louise A Elliott, Francesco Caiazza, Aonghus Lavelle, Donal Maguire, Emir Hoti, Niamh Nolan, Justin G Geoghegan, Elizabeth J Ryan, Cliona O'Farrelly
BACKGROUND: Hepatic immunity, normally protective against neoplasia, is subverted in colorectal liver metastasis (CRLM). Here, we compare the inflammatory microenvironment of CRLM-bearing liver tissue to donor liver. METHODS: Twenty-five patients undergoing resection for CRLM were recruited, 13 of whom developed intrahepatic recurrence within 18 months. Biopsies were obtained from tumour and normal liver tissue adjacent to and distal from, the tumour. Donor liver biopsies were obtained during transplantation...
March 23, 2018: Cancer Immunology, Immunotherapy: CII
https://www.readbyqxmd.com/read/29559973/characterizing-the-role-of-monocytes-in-t-cell-cancer-immunotherapy-using-a-3d-microfluidic-model
#20
Sharon Wei Ling Lee, Giulia Adriani, Erica Ceccarello, Andrea Pavesi, Anthony Tanoto Tan, Antonio Bertoletti, Roger Dale Kamm, Siew Cheng Wong
In the hepatitis B virus (HBV)-related hepatocellular carcinoma tumor microenvironment (TME), monocytes reportedly impede natural T cell functions via PD-L1/PD-1 signaling. However, it remains unclear if T cell receptor-redirected T cells (TCR T cells) are similarly inhibited. Hence, we developed a 3D intrahepatic TME microfluidic model to investigate the immunosuppressive potential of monocytes toward HBV-specific TCR T cells and the role of PD-L1/PD-1 signaling. Interestingly, in our 3D static microfluidic model, we observed that monocytes suppressed only retrovirally transduced (Tdx) TCR T cell cytotoxicity toward cancer cells via PD-L1/PD-1, while mRNA electroporated (EP) TCR T cell cytotoxicity was not affected by the presence of monocytes...
2018: Frontiers in Immunology
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