Human liver cell cultivation for long-term in vitro toxicity studies in a miniaturized multi-compartment 3D bioreactor system

2011 ◽  
Vol 49 (01) ◽  
Author(s):  
SA Hoffmann ◽  
M Lübberstedt ◽  
U Müller-Vieira ◽  
D Knobeloch ◽  
A Nüssler ◽  
...  
Keyword(s):  
Liver Cell ◽  
Human Liver ◽  
In Vitro Toxicity ◽  
Cell Cultivation ◽  
Toxicity Studies ◽  
Human Liver Cell ◽  
Bioreactor System

scholarly journals In Vitro Toxicity Assessment of Amphiphillic Polymer-Coated CdSe/ZnS Quantum Dots in Two Human Liver Cell Models

ACS Nano ◽  
2012 ◽  
Vol 6 (11) ◽  
pp. 9475-9484 ◽  
Author(s):  
Wesley E. Smith ◽  
Jessica Brownell ◽  
Collin C. White ◽  
Zahra Afsharinejad ◽  
Jesse Tsai ◽  
...  
Keyword(s):  
Quantum Dots ◽  
Liver Cell ◽  
Human Liver ◽  
Toxicity Assessment ◽  
In Vitro Toxicity ◽  
Cell Models ◽  
Human Liver Cell ◽  
In Vitro Toxicity Assessment

In vitro toxicity of 7H-dibenzo[c,g]carbazole in human liver cell lines

2002 ◽  
Vol 16 (3) ◽  
pp. 235-243 ◽  
Author(s):  
T. O'Brien ◽  
J. Schneider ◽  
D. Warshawsky ◽  
K. Mitchell
Keyword(s):  
Cell Lines ◽  
Liver Cell ◽  
Human Liver ◽  
In Vitro Toxicity ◽  
Human Liver Cell

In vitro effects of estetrol on receptor binding, drug targets and human liver cell metabolism

Climacteric ◽  
2008 ◽  
Vol 11 (sup1) ◽  
pp. 64-68 ◽  
Author(s):  
M. Visser ◽  
J.-M. Foidart ◽  
H. J. T. Coelingh Bennink
Keyword(s):  
Receptor Binding ◽  
Liver Cell ◽  
Human Liver ◽  
Drug Targets ◽  
Cell Metabolism ◽  
Human Liver Cell ◽  
In Vitro Effects

scholarly journals Comparing in vitro human liver models to in vivo human liver using RNA-Seq

2020 ◽  
Author(s):  
Rajinder Gupta ◽  
Yannick Schrooders ◽  
Duncan Hauser ◽  
Marcel van Herwijnen ◽  
Wiebke Albrecht ◽  
...  
Keyword(s):  
Liver Cell ◽  
Liver Tissue ◽  
Hepg2 Cells ◽  
Human Liver ◽  
Rna Seq ◽  
Cell Models ◽  
Human Liver Tissue ◽  
Human Liver Cell

Abstract The liver plays an important role in xenobiotic metabolism and represents a primary target for toxic substances. Many different in vitro cell models have been developed in the past decades. In this study, we used RNA-sequencing (RNA-Seq) to analyze the following human in vitro liver cell models in comparison to human liver tissue: cancer-derived cell lines (HepG2, HepaRG 3D), induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs), cancerous human liver-derived assays (hPCLiS, human precision cut liver slices), non-cancerous human liver-derived assays (PHH, primary human hepatocytes) and 3D liver microtissues. First, using CellNet, we analyzed whether these liver in vitro cell models were indeed classified as liver, based on their baseline expression profile and gene regulatory networks (GRN). More comprehensive analyses using non-differentially expressed genes (non-DEGs) and differential transcript usage (DTU) were applied to assess the coverage for important liver pathways. Through different analyses, we noticed that 3D liver microtissues exhibited a high similarity with in vivo liver, in terms of CellNet (C/T score: 0.98), non-DEGs (10,363) and pathway coverage (highest for 19 out of 20 liver specific pathways shown) at the beginning of the incubation period (0 h) followed by a decrease during long-term incubation for 168 and 336 h. PHH also showed a high degree of similarity with human liver tissue and allowed stable conditions for a short-term cultivation period of 24 h. Using the same metrics, HepG2 cells illustrated the lowest similarity (C/T: 0.51, non-DEGs: 5623, and pathways coverage: least for 7 out of 20) with human liver tissue. The HepG2 are widely used in hepatotoxicity studies, however, due to their lower similarity, they should be used with caution. HepaRG models, iPSC-HLCs, and hPCLiS ranged clearly behind microtissues and PHH but showed higher similarity to human liver tissue than HepG2 cells. In conclusion, this study offers a resource of RNA-Seq data of several biological replicates of human liver cell models in vitro compared to human liver tissue.

In vitro kinetics of amiodarone and its major metabolite in two human liver cell models after acute and repeated treatments

2015 ◽  
Vol 30 (1) ◽  
pp. 36-51 ◽  
Author(s):  
Giuliana Pomponio ◽  
Camille C. Savary ◽  
Céline Parmentier ◽  
Frederic Bois ◽  
André Guillouzo ◽  
...  
Keyword(s):  
Liver Cell ◽  
Human Liver ◽  
Major Metabolite ◽  
Cell Models ◽  
Human Liver Cell ◽  
Kinetics Of ◽  
In Vitro Kinetics

scholarly journals The Factor VIII Variant X5 Enhances Hemophilia a Gene Therapy Efficiency By Its Improved Secretion

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3356-3356
Author(s):  
Franziska Horling ◽  
Johannes Lengler ◽  
Wenjing Cao ◽  
Biao Dong ◽  
Bagirath Gangadharan ◽  
...  
Keyword(s):  
Gene Therapy ◽  
Factor Viii ◽  
Liver Cell ◽  
Human Liver ◽  
Hemophilia A ◽  
Employment Equity ◽  
Fviii Activity ◽  
Human Liver Cell ◽  
Equity Ownership

Introduction. Adeno-associated virus (AAV)-based factor VIII (FVIII) gene therapy holds great promise to provide clinical benefit in patients with hemophilia A. However, very high doses are currently needed to achieve therapeutic factor levels and the durability appears to be limited to a couple of years. Vector efficiency could be improved by employing more potent liver-specific promoters, but this might come at the price of overstraining the cellular protein folding capacity, causing FVIII to misfold in the lumen of the Endoplasmic Reticulum (ER). This event would in turn activate the unfolded protein response, cause oxidative stress, and if not resolved may even induce cell death. Aims. The objective of the presented study was to test whether the B-domain deleted (BDD)-FVIII-X5 variant can overcome the secretion challenge of high level FVIII expression in the context of hepatic gene therapy. Methods. The human FVIII variant BDD-FVIII-X5 harboring 5 amino acid exchanges in the A1 domain was previously isolated in a screen aimed at identifying those residues in porcine FVIII that are critical for efficient secretion. BDD-FVIII and BDD-FVIII-X5 were produced in Chinese Hamster Ovary (CHO) cells and purified to apparent homogeneity using standard procedures. The preparations were assayed for total protein by UV absorbance at 280 nm and FVIII activity by a chromogenic assay. Both FVIII variants were vectorized using AAV8 and tested in the human liver cell line HepG2 and FVIII knockout mice (E17) at various doses. Resulting samples were assayed for FVIII chromogenic activity. The potential immunogenic risk was evaluated in three hemophilic mouse strains (E17, human FVIII transgenic, humanized HLA-DRB1*1501). Results. A characterization of purified recombinant Refacto-like BDD-FVIII and the corresponding X5 variant revealed similarity of the two proteins and their specific activities in particular, indicating that introduction of the 5 amino acids from porcine FVIII did not alter functionality of human BDD-FVIII. In vitro expression of BDD-FVIII-X5 in a human liver cell line resulted in substantially increased FVIII activity levels in the supernatant compared with the non-modified BDD-FVIII, commensurate with enhanced secretion of the X5 variant. Intravenous delivery of liver-targeted AAV8 vectors carrying the BDD-FVIII-X5 transgene achieved substantial increases in plasma coagulation activity over BDD-FVIII in FVIII-deficient mice, even when highly efficient codon-optimized F8 nucleotide sequences were employed. Evaluation of the immunogenicity of the BDD-FVIII-X5 variant by an immunological risk assessment did not reveal any increased immunogenic risk compared to BDD-FVIII. Conclusions: The fully active BDD-FVIII-X5 variant demonstrated improved secretion in vitro and in vivo, resulting in substantially higher FVIII levels in a hemophilia A mouse model. No signs of enhanced immunogenicity were noted in a comparative immunogenicity study. The results obtained warrant further exploration of the BDD-FVIII-X5 variant for a next generation hemophilia A gene therapy. Disclosures Horling: Baxalta Innovations GmbH, a Takeda company: Employment. Lengler:Baxalta Innovations GmbH, a Takeda company: Employment. Gangadharan:Baxalta Innovations GmbH, a Takeda company: Employment. De La Rosa:Baxalta Innovations GmbH, a Takeda company: Employment, Equity Ownership. Hoellriegl:Baxalta Innovations GmbH, a Takeda company: Employment, Equity Ownership. Reipert:Baxalta Innovations GmbH, a Takeda company: Employment, Equity Ownership. Scheiflinger:Baxalta Innovations GmbH, a Takeda company: Employment, Equity Ownership. Xiao:Ivygen: Other: Patent application on FVIII-X5 has been submitted. Rottensteiner:Baxalta Innovations GmbH, a Takeda company: Employment, Equity Ownership.

scholarly journals Synthesis, in vitro anticancer screening and radiosensitizing evaluation of some new 4-[3-(substituted)thioureido]-N-(quinoxalin-2-yl)-benzenesulfonamide derivatives

2011 ◽  
Vol 61 (4) ◽  
pp. 415-425 ◽  
Author(s):  
Mostafa Ghorab ◽  
Fatma Ragab ◽  
Helmy Heiba ◽  
Marwa El-Gazzar ◽  
Mostafa El-Gazzar
Keyword(s):  
Antitumor Activity ◽  
Anticancer Activity ◽  
Liver Cell ◽  
Human Liver ◽  
Biological Activities ◽  
Γ Irradiation ◽  
Reference Drug ◽  
Human Liver Cell ◽  
Quinoxaline Derivatives

Synthesis, in vitro anticancer screening and radiosensitizing evaluation of some new 4-[3-(substituted)thioureido]-N-(quinoxalin-2-yl)-benzenesulfonamide derivatives Sulfonamides and quinoxaline derivatives possess many types of biological activities and have been recently reported to show substantial antitumor activity. This paper reports the synthesis of novel thioureido sulfaquinoxaline derivatives. All the newly synthesized compounds were evaluated for their in vitro anticancer activity against a human liver cell line (HEPG2) and showed higher activity than the reference drug doxorubicin. 4-(3-(4-Ethylbenzoate) thioureido)-N-(quinoxalin-2-yl)benzenesulfonamide (9) (IC50 = 15.6 μmol L-1), N-(pyridin-2-yl)-4-(3-(4-(N-quinoxalin-2-yl-sulfamoyl)phenyl)thioureido)benzenesulfonamide (10) (IC50 = 26.8 μmol L-1) and N-(quinoxalin-2-yl)-4-(3-(4-(N-thiazol-2-ylsulfamoyl)phenyl)thioureido)benzenesulfonamide (11) (IC50 = 24.4 μmol L-1) were the most potent compared to doxorubicin (IC50 = 71.8 μmol L-1). The most potent compounds 9, 10 and 11 were evaluated as radiosensitizing agents by subjecting the compounds to γ-irradiation (8 kGy).

431 AUTOCRINE AND PARACRINE EFFECTS OF WNT SIGNALING ON HUMAN LIVER CELL TYPES IN VITRO

2012 ◽  
Vol 56 ◽  
pp. S171
Author(s):  
A. Schulze ◽  
U. Ruedrich ◽  
N. Fekete ◽  
R. Gutierrez Jauregui ◽  
M. Ott ◽  
...  
Keyword(s):  
Wnt Signaling ◽  
Liver Cell ◽  
Human Liver ◽  
Cell Types ◽  
Paracrine Effects ◽  
Human Liver Cell
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