Alternative to primary human hepatocytes hepatocytes. Medical search. Frequent questions

Direct protein quantification was applied successfully to study in vitro induction in sandwich cultured primary hepatocytes in a 24-well format using the prototypical inducers rifampicin, omeprazole, and phenobarbital. (aspetjournals.org)
We conclude that targeted absolute LC-MS/MS quantification of drug-metabolizing enzymes and transporters can broaden the scope and significantly increase the impact of in vitro drug metabolism studies, such as induction, as an important supplement or future alternative to mRNA and activity data. (aspetjournals.org)
Common culture formats used for in vitro enzyme induction studies comprise conventional and sandwich cultures, the former referring to plated hepatocytes maintained on rigid substratum (e.g., collagen), whereas in the latter cells are "sandwiched" by an additional layer of either collagen or a composite of extracellular matrix proteins, such as Matrigel ( LeCluyse, 2001 ). (aspetjournals.org)
The protocol resulted in cells that had a better resemblance to primary human hepatocytes than protocols described previously, showing a good potential to use them as an alternative to primary cells for in vitro modeling. (biolamina.com)
As an alternative tool, they investigate the sensitivity and predictivity of the in-vitro alkaline comet assay with different liver cell models (HepG2 cells, primary rat and human hepatocytes). (fraunhofer.de)
The various areas that he examines in his Pharmacology study include Metabolite, In vitro, Biochemistry and Hepatocyte. (research.com)
Activity of CAR-grafted T cells was evaluated in vitro against HCV/E2-transfected cells as well as hepatocytes infected with cell culture-derived HCV (HCVcc). (uninsubria.it)
But even with published protocols readily available, creating your own in-house 3D models remains expensive, time consuming, and difficult to master," adds InSphero CEO and co-founder Jan Lichtenberg, PhD. "We are excited to foster development of safer drugs by making our high-quality, industry-grade 3D human in vitro liver models more accessible and affordable. (insphero.com)
Through partnerships, InSphero supports pharmaceutical and biotechnology researchers in successful decision-making by accurately rebuilding the human physiology in vitro . (insphero.com)
Although liver failure can be treated via hepatocyte transplantation, it also faces multiple problems comprising the shortage of high-quality hepatocytes sources, rejection of allogeneic transplants, difficulty to expand, and losing hepatic characteristics in vitro [ 7 , 8 ]. (springer.com)
Previous studies have proven that rodent and human MSCs can differentiate into HLCs in vitro and in vivo , which is one of the mechanisms of MSCs in the treatment of liver failure. (springer.com)
Recent studies have provided increasing evidence that hepatocytes with different ploidy statuses behave differently in a context-dependent manner (eg, susceptibility to oncogenesis, regenerative ability after injury, and in vitro proliferative capacity). (bvsalud.org)
We have recently demonstrated that a natural dietary supplement BreastDefend (BD), which contains extracts from medicinal mushrooms (Coriolus versicolor, Ganoderma lucidum, Phellinus linteus), medicinal herbs (Scutellaria barbata, Astragalus membranaceus, Curcuma longa), and purified biologically active nutritional compounds (diindolylmethane and quercetin), inhibits proliferation and metastatic behavior of MDA-MB-231 invasive human breast cancer cells in vitro. (spandidos-publications.com)
BreastDefend™ (BD) is a polybotanical dietary supplement which inhibits growth and invasive behavior of highly metastatic human breast cancer cells in vitro ( 6 ). (spandidos-publications.com)
These in vitro, and their expression in these human tumour virus. (who.int)

Human-derived hepatic cell lines are a valuable alternative to primary hepatocytes for drug metabolism, transport and toxicity studies. (cancerindex.org)
3) Developing surgical strategies for efficient orthotopic engraftment of hepatocytes and hepatic organoids into the liver. (ucsf.edu)
Acetaminophen (APAP) poisoning is one of the leading causes of acute hepatic failure and liver transplantation is often the only lifesaving alternative. (mdpi.com)
The action of antidiabetic plants of the Canadian James Bay Cree traditional pharmacopeia on key enzymes of hepatic glucose homeostasis ") report the antidiabetic action of seven Canadian plants as evidenced by glucose-6-phosphatase and glycogen synthase, two key enzymes, respectively, involved in gluconeogenesis and glycogenesis in hepatocytes. (hindawi.com)
Because all coagulation factors are made in the liver (by hepatocytes and hepatic sinusoidal endothelial cells), both the prothrombin time (PT) and partial thromboplastin time (PTT) are prolonged in severe liver disorders. (msdmanuals.com)

In general, P450 and UGT expression was lower in hepatocyte cultures than that in liver, and CYP2C9 was found to be the most abundant P450 isoform expressed in cultured hepatocytes. (aspetjournals.org)
Protein expression and function of organic anion transporters in short-term and long-term cultures of Huh7 human hepatoma cells. (cancerindex.org)
Primary human hepatocytes were cultured on collagen pre-coated sensor chips or in conventional two-dimensional cultures in chemically defined Human Hepatocyte Maintenance Medium. (altex.org)
In conventional cultures of human hepatocytes, AAP had no effect on cellular viability. (altex.org)
The half-life of duck hepatitis B virus supercoiled DNA in congenitally infected primary hepatocyte cultures. (wort-liebe.com)

Though the current process for toxicity testing largely evolves around the use of in vivo animal work, more and more studies rely on human induced pluripotent stem cell (iPSC)-derived hepatocytes as a viable and up-and-coming alternative of determining toxicity. (enzolifesciences.com)
Induced pluripotent stem cell-derived hepatocytes have a primary tissue-like phenotype, constant and indefinite disposal, and the potential to establish genotype-specific cells from different individuals, which make them an interesting means of predicting drug-induced toxicity. (enzolifesciences.com)
Moving to the future where we are much less reliant on detailed, multi-endpoint toxicity evaluations, these short-term in life transcriptomic studies will be an important linchpin allowing comparisons across MOA-oriented in life studies and emerging high throughput gene expression studies in cell lines and primary cells. (scitovation.com)

Assay conditions, such as culture format and duration, media supplements etc., were reported previously to alter the phenotype and induction response of cultured hepatocytes ( LeCluyse, 2001 ). (aspetjournals.org)
Donald Tweedie, PhD and Ed LeCluyse, PhD continue their former discussion on the challenges and opportunities with using primary human hepatocytes in drug development. (lnhlifesciences.org)
Drs. Tweedie and LeCluyse have a combined 70 years' experience in drug development and research involving alternative drug metabolism and toxicological methods. (lnhlifesciences.org)

The sandwich culture format and 0.1 μM DEX in media retained the protein expression in the hepatocytes closest to the levels found in liver. (aspetjournals.org)
It also binds strongly to a protein at ~55 kDa in human lung tissue extracts, which we believe represents a glycosylated form of IL6. (abcam.com)
Recombinant full length protein corresponding to Human IL-6. (abcam.com)
Despite the massive reduction of Dio1 and Sepp1 mRNAs, significantly more corresponding protein was detected in primary hepatocytes lacking Secisbp2 than in cells lacking tRNA[Ser]Sec. Regarding selenoprotein expression, compensatory nuclear factor, erythroid-derived, like 2 (Nrf2)-dependent gene expression, or embryonic development, phenotypes were always milder in Secisbp2-deficient than in tRNA[Ser]Sec-deficient mice. (nih.gov)

We compared the response of primary human hepatocytes from two donors with primary rat hepatocytes and the cell line HepG2 to the test compound acetaminophen (AAP) by measuring oxygen consumption, extracellular acidification and cell adhesion as dynamic parameters of cell metabolism. (altex.org)
Cell respiration was inhibited by AAP concentrations of 500 mg/l and more in all three cell types, whereas only the cellular acidification rates and cell adhesion of the rat hepatocytes and the HepG2 cells were affected by AAP. (altex.org)

This study describes a robust and scalable protocol for pluripotent stem cell (PSC) differentiation into high-quality bipotent hepatoblasts and hepatocyte-like cells (HLCs), with Biolaminin 521 (laminin-521) as the cell culture matrix. (biolamina.com)
Transcript-specific and gender-selective effects on selenoprotein mRNA abundance were greater in Secisbp2-deficient hepatocytes than in tRNA[Ser]Sec-deficient cells. (nih.gov)
MultiOMICs landscape of SARS-CoV-2-induced host responses in human lung epithelial cells. (helsinki.fi)
Here, we explain the FAL's research into the liver and how its researchers use human cells to model liver disease. (frame.org.uk)
To model this process, the FAL uses all the primary human cells involved in the liver, including hepatocyte cells, Kupffer cells, stellate cells and cells with liver disease (fibrosis), all derived from liver samples which are ethically sourced from hospitals in the East Midlands region. (frame.org.uk)
As the liver has a remarkable capacity to regenerate, the FAL is also isolating the cells it believes are adult stem cells and is growing and differentiating these to produce hepatocytes. (frame.org.uk)
The FAL then produces 'scaffolding' from donated human liver tissue that has had the original cells removed. (frame.org.uk)
Background and objectives of the study: This master's thesis consists of three parts involving induced pluripotent stem cell-derived hepatocyte-like cells (iPSC-HLCs). (tuni.fi)
To this end we have used chimeric antigen receptors (CARs), a very promising approach recently used in several clinical trials to redirect primary human T cells against different tumours. (uninsubria.it)
Results: In this proof-of-concept study, retrovirus-transduced human T cells expressing anti-HCV/E2 CARs were endowed with specific antigen recognition accompanied by degranulation and secretion of proinflammatory and antiviral cytokines, such as interferon gamma, interleukin 2 and tumour necrosis factor a. (uninsubria.it)
InSphero's proprietary production technology utilizes primary hepatocytes from multiple human donors in co-culture with Kupffer cells and liver endothelial cells to produce 3D liver models with highly standardized drug response from batch to batch that capture inflammation-related toxic effects standard, hepatocyte-only spheroids miss. (insphero.com)
MSCs have the capacity of multiple differentiations and self-renewal and have been proven to be able to differentiate into a series of cell lineages, such as adipocytes, osteoblasts, chondroblasts, and hepatocyte-like cells (HLCs). (springer.com)
In the present study, we evaluated whether BD suppresses growth and breast-to lung cancer metastasis in an orthotopic model of human breast cancer cells implanted in mice. (spandidos-publications.com)
that is histopathological y very simi- T cel s, B cel s, natural kil er cel s, LMP1 of EBV can transform ro- lar to that caused by hepatitis B vi- macrophages, and dendritic cells, dent fibroblasts and is expressed rus (HBV) in humans, but it does so and this humanized mouse model in most of the human cancers as- through a different mechanism. (who.int)

PSC-derived hepatoblasts were able to mature into hepatocytes and bile ducts within syngeneic liver organoids. (biolamina.com)
2) Elucidating the importance of dimensionality in promoting the generation of highly-functional human stem cell-derived liver organoids. (ucsf.edu)

Selenoproteins contain the rare amino acid selenocysteine (Sec). Mutations in SECISBP2 in humans lead to reduced selenoprotein expression thereby affecting thyroid hormone-dependent growth and differentiation processes. (nih.gov)
Andreas K. Nussler interconnects Cellular differentiation, Hepatocyte, Induced pluripotent stem cell, DNA demethylation and Mesenchymal stem cell in the investigation of issues within Stem cell. (research.com)

Sensor chip-based results were compared with conventional assays for hepatocytes like albumin release and urea release. (altex.org)
For several of the human tu- and various assays demonstrated an sues. (who.int)

We establish and characterize the Bckdha ( branched chain keto acid dehydrogenase a ) −/− mouse that exhibits a lethal neonatal phenotype mimicking human MSUD. (nature.com)

ab6672 detects a band at 25 kDa in human lung tissue lysate and mouse spleen tissue lysate, however the signal in mouse tissue is significantly lower. (abcam.com)
ab6672 also detects several bands in human lung tissue lysate within the region of 30-40 kDa. (abcam.com)
We found significantly higher GLUT1 mRNA expression levels in HCC tissues and cell lines compared with primary human hepatocytes and matched nontumor tissue. (uni-regensburg.de)
Its robust and precisely engineered suite of 3D InSight™ human tissue platforms are used by major pharmaceutical companies worldwide to increase efficiency in drug discovery and safety testing. (insphero.com)

Immunohistochemical staining of human liver shows moderate cytoplasmic positivity in hepatocytes. (atlasantibodies.com)

In the lung styrene had enrichment for cell cycle pathways but not cytotoxicity [12] and methylene chloride had enrichment for organelle biogenesis, TCA cycle, and respiratory electron transport indicating primary effects through a metabolite, carbon monoxide [14]. (scitovation.com)

His research program has included studies using primary and immortalized rodent and human cell lines, transgenic rodent models, and molecular genetic approaches to examine mechanisms and identify biomarkers of cytotoxicity, genotoxicity, and mutagenicity at the molecular, cellular, and animal level. (scitovation.com)

2020) Identifying qualitative differences in PPARalpha signaling networks in human and rat hepatocytes and their significance for next generation chemical risk assessment methods. (scitovation.com)
BACKGROUND & AIMS: There is a long-standing debate regarding the biological significance of polyploidy in hepatocytes. (bvsalud.org)
LOAELs or NOAELs should also help in determining whether or not the effects vary with dose and/or duration, and place into perspective the possible significance of these effects to human health. (cdc.gov)

Cultured hepatocytes offer the possibility to assess long-term effects, such as enzyme induction (i.e., changes of the expression levels of molecular entities of the hepatocytes). (aspetjournals.org)
Molecular mechanisms underlying the enhanced functions of three-dimensional hepatocyte aggregates. (ucsf.edu)
Scholarly interests include investigation of molecular markers of human disease that provide diagnostic function, serve as targets for possible therapeutic manipulation, or provide insight into mechanisms of human disease. (stanford.edu)

Design: Anti-HCV/E2 CARs were composed of single-chain variable fragments (scFvs) obtained from a broadly cross-reactive and cross-neutralising human monoclonal antibody (mAb), e137, fused to the intracellular signalling motif of the costimulatory CD28 molecule and the CD3 zeta domain. (uninsubria.it)

Scientists with CPSC , FDA , and NIEHS and collaborators compiled such a data set for human skin sensitization potential by collecting data from the scientific literature for human predictive patch tests that used the human maximization or human repeated insult patch test protocols. (nih.gov)

These guidelines update previous CDC recommendations for the diagnosis, treatment, and prevention of tuberculosis (TB) among adults and children coinfected with human immunodeficiency virus (HIV) in the United States. (cdc.gov)
These guidelines update previous CDC recommendations for treating and preventing active tuberculosis (TB) among adults and children coinfected with human immunodeficiency virus (HIV) (1-3). (cdc.gov)

Moreover, The use of animals as surrogate rine host, can provide a platform for animal models for tumour viruses in hosts for the study of human tu- in vivo infection. (who.int)
For instance, mice are able to reconstitute most lymphomas in monkeys and humans woodchuck hepatitis virus induces major components of the human provides strong support for a direct hepatocellular carcinoma (HCC) haematolymphoid system including oncogenic role of EBV in vivo. (who.int)

The levels of metabolizing enzymes and transporters expressed in hepatocytes are decisive factors for hepatobiliary disposition of most drugs. (aspetjournals.org)

Chronic INH hepatotoxicity results in the induction of hepatocyte apoptosis, with associated disruption of mitochondrial membrane potential and DNA strand breaks. (medscape.com)

One exception is hu- humanized SCID mice, the use of al oncogenic viruses that are strictly man T-cell lymphotropic virus type 1 surrogate hosts has not proven very species-specific, causing cancer in (HTLV-1): in addition to its ability to useful for defining tumour site con- humans only. (who.int)
In this combined immunodeficiency (SCID) cancer is low in these species (as it chapter, some aspects of this issue mice, in which the human target is in humans), which renders cancer are discussed. (who.int)

This price decrease makes InSphero's pharma-validated human liver toxicology model and highly efficient Akura™ plate technology more accessible to researchers in industry and academia as a cost-effective alternative to do-it-yourself approaches. (insphero.com)
The world's first and only 3D human liver spheroid models for toxicology and safety testing shipped directly to laboratories throughout North America, Europe, and Japan, 3D InSight™ Human Liver Microtissues are the gold standard for drug-induced liver injury (DILI) evaluation. (insphero.com)
He explained, "I am very excited to become part of the ScitoVation team known for its scientific excellence and to lead ScitoVation in developing new alternative methodologies (NAM) to reduce, refine and replace the use of animals in toxicology with non-animal human-relevant biological systems. (scitovation.com)
Dr. Leslie Recio's extensive experience in toxicology research and commitment to New Approach Methods (NAM) will strengthen ScitoVation's position as a pioneer in developing and promoting alternative methodologies that reduce reliance on animal testing and focus on human-relevant biological systems. (scitovation.com)
The primary purpose of this chapter is to provide public health officials, physicians, toxicologists, and other interested individuals and groups with an overall perspective on the toxicology of methoxychlor. (cdc.gov)

Immunocytochemistry/ Immunofluorescence: SR-BI Antibody [NB400-104] - SR-BI antibody was tested in human fibroblast samples fixed in 4% PFA and permeabilized in PBS (0.2% Tween). (novusbio.com)
For other human tumour virus- primate species are related to the hu- tween data in humans and in experi- es, the use of humanized severe man tumour viruses, the incidence of mental animals is not obvious. (who.int)

It is not indicated if an acceptable alternative is available or if contraindications are present (eg, some cases of malignancy, terminal conditions, poor expected quality of outcome). (medscape.com)
Transplantation is not indicated if an acceptable alternative is available or if contraindications, such as malignancy, a terminal condition, or poor expected outcome exist. (medscape.com)

Animal studies take more time and money than do stem cell testing and they lack the reproducibility of results in human models. (enzolifesciences.com)
Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk. (medscape.com)
From forced expression studies in both cell lines and primary turned ON/OFF. (lu.se)

The use of hepatocytes provides, among others, the advantage of including active drug transport mechanisms as well as effects of drug metabolites that are formed during the experimental incubation period by phase I and II metabolism. (aspetjournals.org)

2014) A map of the PPARalpha transcription regulatory network for primary human hepatocytes. (scitovation.com)
Because humans are the primary subject of interest for regulatory safety testing, it is advantageous to have human reference data available for evaluation of NAMs for assessing chemical safety. (nih.gov)

In hepatocyte-specific conditional mouse models, Secisbp2 gene inactivation is less detrimental than tRNA[Ser]Sec inactivation. (nih.gov)
Funded by an annual grant made by FRAME to support its work, the FAL is based at the University of Nottingham Medical School and aims to produce human-based research systems for medical research that are better and more relevant to humans than current animal models. (frame.org.uk)
Differences in the corresponding DNA repair processes are investigated by using repair-proficient as well as repair-deficient human and mouse cell models. (fraunhofer.de)
The rapidly growing demand for 3D liver models has fuelled innovation throughout our company-from R&D to operations," says InSphero CBO Frank Junker, PhD. "With our upgraded production and logistics processes for 3D InSight™ Human Liver Microtissue, we can now capitalize on efficiencies honed over the past decade. (insphero.com)
More recently Dr. Recio has been committed to developing New Approach Methods to replace or reduce the reliance on animal testing by developing genotoxicity assessments in human hepatocyte models. (scitovation.com)
Animal models for human tumour mental animals is not easy to answer does induce adult T-cell leukaemia/ viruses that make use of animal virus- for these agents, because cancer bi- lymphoma (ATLL), albeit in monkeys es are scarce. (who.int)

Alternative splicing of this gene results in multiple transcript variants. (cancerindex.org)
First promising results have already been obtained with primary hepatocytes. (fraunhofer.de)

Physiological ranges of matrix rigidity modulate primary mouse hepatocyte function in part through hepatocyte nuclear factor 4 alpha. (ucsf.edu)

First, there is great clinical need to develop alternative therapies for end stage liver disease, which is currently treated by liver transplantation and severely limited by the shortage of donor organs. (ucsf.edu)
The present invention provides a simple and robust human liver cell-based system in which persistent hepatitis C infection, persistent hepatitis B infection or ethanol exposure induces a clinical Prognostic Liver Signature (PLS) high-risk gene signature. (sumobrain.com)
Reduction of total cholesterols (TC) and LDL-C by dietary alterations and medications that affect lipid metabolism [ 14 ] is found to reduce the occurrence of atherosclerosis in animals and clinical cardiovascular events in human [ 15 ]. (hindawi.com)

Biobanks are becoming a valuable and popular alternative source for exploring scientific ideas, mechanism of diseases and testing new bioactive compounds and biologicals, with the minimal possible discomfort of the animals and at low costs. (bprc.nl)

BPRC's Primate Biobank is the biggest non-human primate bank in Europe. (bprc.nl)

European Medicine Agency, Draft Guideline on the Investigation of Drug Interactions ( http://www.ema.europa.eu/docs/en_GB/document_library/Scientific_guideline/2010/05/WC500090112.pdf ]. (aspetjournals.org)

Animal test alternatives: Refinement, reduction, replacement. (cdc.gov)
NLM developed ALTBIB to provide access to PubMed citations for users seeking information on alternatives to animal testing. (nih.gov)

Animals were treated at P0 with intravenous human BCKDHA AAV8 vectors under the control of either a ubiquitous or a liver-specific promoter. (nature.com)
Public health officials and others concerned with appropriate actions to take at hazardous waste sites may want information on levels of exposure associated with more subtle effects in humans or animals (LOAELs) or exposure levels below which no adverse effects (NOAELs) have been observed. (cdc.gov)
For this reason, the infect humans, this virus can infect cordance between humans and ex- question about tumour site concor- several other species - including perimental animals. (who.int)

[ 4 ] Acute liver failure from hemochromatosis, leading to a histologic diagnosis of giant-cell hepatitis, is the primary indication for liver transplantation in the neonatal population. (medscape.com)

Although Western medicines have been the dominant treatment used by hyperlipidemic patients, their adverse effects and part of patients' intolerance to the pharmacotherapy make traditional Chinese medicine (TCM) one of their alternatives. (hindawi.com)

Here, we report the use of a targeted liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) method for concurrent quantification of multiple cytochrome P450 (P450), UDP-glucuronosyltransferase (UGT), and transporter proteins in cultured primary human hepatocytes. (aspetjournals.org)

Genetic and environmental factors are the primary causes of diabetes. (hindawi.com)

Anatomy16

Organisms12

Diseases9

Chemicals and Drugs87

Analytical, Diagnostic and Therapeutic Techniques and Equipment23

Phenomena and Processes37

Disciplines and Occupations1

Information Science3

Vitro15

Hepatic5

Cultures5

Toxicity3

LeCluyse3

Protein4

HepG22

Cells14

Organoids2

Differentiation2

Assays2

Phenotype1

Tissue4

Immunohistochemical1

Metabolite1

Rodent and human1

Significance3

Molecular3

Monoclonal antibody1

Protocols1

Immunodeficiency virus2

Vivo2

Enzymes1

Induction1

Mice2

Toxicology5

Tween2

Contraindications2

Studies3

Incubation1

Regulatory2

Models6

Results2

Mouse1

Clinical3

Diseases1

Primate1

Scientific1

Animal2

Animals3

Neonatal1

Effects1

Multiple1

Factors1