Abstract：
:Liver disease is an escalating global health issue. While liver transplantation is an effective mode of therapy, patient mortality has increased due to the shortage of donor organs. Developing renewable sources of human liver tissue is therefore attractive. Pluripotent stem cell-derived liver tissue represents a potential alternative to cadaver derived hepatocytes and whole organ transplant. At present, two-dimensional differentiation procedures deliver tissue lacking certain functions and long-term stability. Efforts to overcome these limiting factors have led to the building of three-dimensional (3D) cellular aggregates. Although enabling for the field, their widespread application is limited due to their reliance on variable biological components. Our studies focused on the development of 3D liver tissue under defined conditions. In vitro generated 3D tissues exhibited stable phenotype for over 1 year in culture, providing an attractive resource for long-term in vitro studies. Moreover, 3D derived tissue provided critical liver support in two animal models, including immunocompetent recipients. Therefore, we believe that our study provides stable human tissue to better model liver biology 'in the dish', and in the future may permit the support of compromised liver function in humans.
journal_name
Arch Toxicoljournal_title
Archives of toxicologyauthors
Rashidi H,Luu NT,Alwahsh SM,Ginai M,Alhaque S,Dong H,Tomaz RA,Vernay B,Vigneswara V,Hallett JM,Chandrashekran A,Dhawan A,Vallier L,Bradley M,Callanan A,Forbes SJ,Newsome PN,Hay DCdoi
10.1007/s00204-018-2280-2subject
Has Abstractpub_date
2018-10-01 00:00:00pages
3117-3129issue
10eissn
0340-5761issn
1432-0738pii
10.1007/s00204-018-2280-2journal_volume
92pub_type
杂志文章abstract：:The mycotoxins altertoxin I and II (ATX I and II) are secondary metabolites produced by Alternaria alternata fungi and may occur as food and feed contaminants, especially after long storage periods. Although the toxic potential of altertoxins has been previously investigated, little is known about the pathways that pl...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-016-1726-7
更新日期：2017-01-01 00:00:00
abstract：:The α,β-unsaturated carbonyl group is recognized as alert for mutagenicity, attributed to (1) its direct reaction with DNA, counteractable by glutathione (GSH), and (2) oxidative stress caused indirectly by GSH depletion. Accordingly, the α,β,γ,δ-unsaturated lactone patulin (PAT), a mycotoxin detected in fruits and pr...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-014-1443-z
更新日期：2016-02-01 00:00:00
abstract：:Treatment of cats with acrylamide, either 7.5 or 15 mg/kg IM, once a day for 10 days, resulted in increases of 31 and 47% in the phospholipid content of sciatic nerve, respectively, from a control level of 41.1 +/- 2.7 mg/kg wet weight. Determination of the distribution of individual phospholipids indicated no signifi...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00316124
更新日期：1984-09-01 00:00:00
abstract：:Interactions between chemicals in a mixture and interactions of mixture components with the skin can significantly alter the rate and extent of percutaneous absorption, as well as the cutaneous disposition of a topically applied chemical. The predictive ability of dermal absorption models, and consequently the dermal ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040100242
更新日期：2001-08-01 00:00:00
abstract：:Cadmium chloride was administered by gavage to female rats 5 days a week for 5 weeks, then during mating and gestation periods at doses of 0.04, 0.4, and 4 mg Cd/kg/day. Treatment with cadmium neither affected the survival and fertility of females, nor produced overt fetotoxic effects. Fetal cadmium concentration was ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01234482
更新日期：1983-12-01 00:00:00
abstract：:2,3,7,8-Tetrachlorodibenzo- p-dioxin (TCDD) is known to influence vitamin A homeostasis. In order to investigate the mechanism behind this retinoid disruption, male Sprague-Dawley rats were exposed to TCDD at doses ranging from 0.1 to 100 micro g/kg body weight, and were killed 3 days after exposure. Additional groups...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-003-0457-8
更新日期：2003-07-01 00:00:00
abstract：:The responsiveness of the hepatic supernatant NAD+-dependent aldehyde dehydrogenase with a high Km value (high Km-AldDH) to phenobarbital (PB) and 3-methylcholanthrene (3-MC) treatment was studied in male rats of three strains; Wistar, Long-Evans, and Sprague-Dawley. A remarkable strain difference in the response of t...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00333620
更新日期：1979-12-01 00:00:00
abstract：:Perfluorooctanoic acid (PFOA) has been shown to cause hepatotoxicity and other toxicological effects. Though PPARα activation by PFOA in the liver has been well accepted as an important mechanism of PFOA-induced hepatotoxicity, several pieces of evidence have shown that the hepatotoxic effects of PFOA may not be fully...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-016-1675-1
更新日期：2017-01-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-014-1303-x
更新日期：2015-09-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-001-0301-y
更新日期：2002-02-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-005-0016-6
更新日期：2006-02-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-004-0562-3
更新日期：2004-08-01 00:00:00
abstract：:Group means from nerve conduction studies of persons exposed to lead were used in a meta-analysis. Differences between the control and exposed groups, and the slopes between nerve conduction measurements and log(10) blood lead concentrations were estimated using mixed models. Conduction velocity was reduced in the med...
journal_title：Archives of toxicology
pub_type： 杂志文章,meta分析
doi：10.1007/s00204-008-0292-z
更新日期：2008-08-01 00:00:00
abstract：:In the present study, spiking was used as a strategy to evaluate the mutagenicity of individual compounds in a mixture. Mutagenicity of individual polycyclic aromatic hydrocarbons (PAH) was evaluated in an organic extract of diesel exhaust particles (DEP). The particles were extracted with dichloromethane (DCM). After...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050555
更新日期：1998-10-01 00:00:00
abstract：:The cholestatic effect of the newly developed oestradiol sulphamate (J995) was compared with that of the natural oestrogen oestradiol (E) and of the cholestatic standard oestrogen ethinyloestradiol (EE). Female ovariectomized rats were orally treated for 7 days with oestrogen doses molar equivalent to 0.01, 0.1, 1, an...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050409
更新日期：1997-01-01 00:00:00
abstract：:Gene expression analysis has been established as a tool for the characterization of genotoxic mechanisms of chemical mutagens. It has been suggested that expression analysis is capable of distinguishing compounds that cause DNA damage from those that interfere with mitotic spindle function. Formaldehyde (FA) is known ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-013-1060-2
更新日期：2013-11-01 00:00:00
abstract：:The cytotoxicity of trivalent and pentavalent inorganic arsenic salts was determined in mouse fibroblasts in vitro. Concentrations of As (III) in the microM range led to a reduction of proliferation and viability with a concomitant increase in LDH release and stimulation of lactic acid production. Similar effects were...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF00290882
更新日期：1985-08-01 00:00:00
abstract：:Concerning molecular and cellular mechanisms of aluminum toxicity, recent studies support the hypothesis that interactions of aluminum ions with elements of signal transduction pathways are apparently primary events in cells. In the case of the phosphoinositide-associated signalling pathway of neuroblastoma cells, gua...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s002040050023
更新日期：1994-01-01 00:00:00
abstract：:The toxic effect of cyclophosphamide on the proliferative cell population of hair follicles plucked from the human scalp was examined by the in vivo nuclear aberration assay. Patients participating in an independent clinical trial received oral low dose cyclophosphamide, intravenous high dose cyclophosphamide or oral ...
journal_title：Archives of toxicology
pub_type： 临床试验,杂志文章,随机对照试验
doi：10.1007/BF01974396
更新日期：1990-01-01 00:00:00
abstract：:A dual-label time-resolved fluoroimmunoassay (TRFIA) for simultaneous quantification of aflatoxin B1 (AFB1) and ochratoxin A (OTA) is described. For this, microtitration wells were coated with AFB1-horse radish peroxidase (HRP) and OTA-bovine serum albumin. The standards and samples were loaded on the coated plates, a...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-009-0410-6
更新日期：2009-06-01 00:00:00
abstract：:Brominated flame retardants (BFRs) are abundant persistent organic pollutants with well-studied toxicity. The toxicological and ecological concerns associated with BFRs argue for replacement by safe(r) alternatives. Though previous research identified the nervous system as a sensitive target organ for BFRs, the (neuro...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-013-1187-1
更新日期：2014-04-01 00:00:00
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journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF01973693
更新日期：1993-01-01 00:00:00
abstract：:During/after the BP/Deepwater Horizon oil spill, cleanup workers, fisherpersons, SCUBA divers, and coastal residents were exposed to crude oil and dispersants. These people experienced acute physiological and behavioral symptoms and consulted a physician. They were diagnosed with petroleum hydrocarbon poisoning and ha...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-015-1526-5
更新日期：2016-04-01 00:00:00
abstract：:Glucose is a major energy source for the entire body, while fructose metabolism occurs mainly in the liver. Fructose consumption has increased over the last decade globally and is suspected to contribute to the increased incidence of non-alcoholic fatty liver disease (NAFLD). NAFLD is a manifestation of metabolic synd...
journal_title：Archives of toxicology
pub_type： 杂志文章,评审
doi：10.1007/s00204-016-1892-7
更新日期：2017-04-01 00:00:00
abstract：:Bolesatine, a glycoprotein from Boletus satanas Lenz, has previously been shown to be mitogenic to rat and human lymphocytes at very low concentrations, whereas higher concentrations inhibit protein synthesis in vitro and in several in vivo systems. The mechanism whereby this mitogenic activity occurs was previously u...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050223
更新日期：1995-01-01 00:00:00
abstract：:Renal papillary necrosis (RPN) was induced in Fischer 344 (F344) rats (n = 4) using 2-bromoethanamine hydrobromide (BEA) dosed at 150 mg/kg, and in multimammate desert mice (Mastomys natalensis) at 150 and 250 mg/kg (n = 4 per group). Control rats and Mastomys were dosed with 0.9% saline (n = 4 per group). Urine was c...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/BF02733668
更新日期：1995-01-01 00:00:00
abstract：:Teratogenic effects caused by a new nitroimidazopyridazine were examined in Wistar (WU) rats after repeated oral administration of 0, 2.5, 10, and 40 mg/kg, given on days 6-17 post coitum (p.c.) (Day of mating = Day 0) in a regular study on embryo-fetal development according to ICH S5A. At day 20 p.c., fetuses were re...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s00204-006-0057-5
更新日期：2006-07-01 00:00:00
abstract：:The aim of this study was to investigate the genotoxic potential of DNA adducts and to compare DNA adduct levels and patterns in petroleum vacuum distillates, coal tar distillate, bitumen fume condensates, and related substances that have a wide range of boiling temperatures. An in vitro assay was used for DNA adduct ...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040000172
更新日期：2001-01-01 00:00:00
abstract：:The release and availability of the carcinogenic component of the soluble azo dye Direct Red 46 and the insoluble azo pigment Pigment Yellow 17 were analyzed in Wistar rats using hemoglobin adducts as a dosimeter. The levels of hemoglobin adducts were found to be very low. Intestinal cleavage and release of 3,3'-dichl...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040050024
更新日期：1994-01-01 00:00:00
abstract：:The toxicity of amphetamines is conditioned by a complex array of mechanisms, involving the increase of neurotransmission (e.g. leading to hyperthermia) and enzymatic and non-enzymatic oxidation of amphetamines and biogenic amines. Considering that all these processes may increase the generation of hydrogen peroxide (...
journal_title：Archives of toxicology
pub_type： 杂志文章
doi：10.1007/s002040100264
更新日期：2001-10-01 00:00:00
