A model combining the whole embryo culture with human liver S-9 fraction for human teratogenic prediction

Zhao, Jia-Xi; Krafft, Nathalie; Terlouw, G.D.C.; Bechter, R.

doi:10.1016/0887-2333(93)90087-l

Cited by 14 publications

(6 citation statements)

References 18 publications

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“…Stem cell‐based assays, as well as other in vitro and ex vivo assays, may be unable to detect proteratogens, as they lack maternal metabolisms. To overcome such limitation, several attempts have been made to augment in vitro or ex vivo assays by incorporating exogenous metabolic systems, such as hepatocytes or liver extracts, to simulate the effects of the maternal liver (Hettwer et al, 2010 ; Luijten, Verhoef, Westerman, & Piersma, 2008 ; Oglesby, Ebron, Beyer, Carver, & Kavlock, 1986 ; Ozolins, Oglesby, Wiley, & Wells, 1995 ; Piersma et al, 1991 ; Zhao, Krafft, Terlouw, & Bechter, 1993 ), although it is unclear how effectively such liver substitutes can represent the complexity of maternal metabolisms. For many pharmaceutical drugs, the information on their metabolisms in the human body is often available through pharmacokinetic studies, including their chemical structures and the plasma concentrations of the major metabolites.…”

Section: Overcoming the Limitations Of Stem Cell Modelsmentioning

confidence: 99%

Toward better assessments of developmental toxicity using stem cell‐based in vitro embryogenesis models

Marikawa

2022

Birth Defects Research

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In the past few decades, pluripotent stem cells have been explored as nonanimal alternatives to assess the developmental toxicity of chemicals. To date, numerous versions of stem cell‐based assays have been reported that are allegedly effective. Nonetheless, none of the assays has become the gold standard in developmental toxicity assessment. Why? This article discusses several issues in the hope of facilitating the refinement of stem cell assays and their acceptance as the cornerstone in predictive developmental toxicology. Each stem cell assay is built on a limited representation of embryogenesis, so that multiple assays are needed to detect the diverse effects of various chemicals. To validate and compare the strengths and weaknesses of individual assays, standardized lists of reference chemicals should be established. Reference lists should consist of exposures defined by toxicokinetic data, namely maternal plasma concentrations that cause embryonic death or malformations, and also by the effects on the molecular machineries that control embryogenesis. Although not entirely replacing human or animal tests, carefully selected stem cell assays should serve as practical and ethical alternatives to proactively identify chemical exposures that disturb embryogenesis. To achieve this goal, unprecedented levels of coordination and conviction are required among research and regulatory communities.

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Section: Overcoming the Limitations Of Stem Cell Modelsmentioning

confidence: 99%

Toward better assessments of developmental toxicity using stem cell‐based in vitro embryogenesis models

Marikawa

2022

Birth Defects Research

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“…Drug metabolism can be mimicked in various ways. A liver homogenate (S9) and appropriate cofactors have been added to the culture medium using liver from different sources like rat (Fantel et al 1979;Kitchin et al 1981) or human (Zhao et al 1993). Oglesby et al(1992) have cocultured hepatocytes during the culture period producing metabolites concurrently in the culture medium.…”

Section: Mammalian Postimplantation Whole Embryo Culturementioning

confidence: 99%

The Validation and Use of In Vitro Teratogenicity Tests

Bechter

1995

Archives of Toxicology

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“…Conspecific or allospecific liver homogenates may be prepared and added to culture medium along with appropriate cofactors. Some of the earliest successful systems employed liver from adult rats that had been preinduced with polychlorinated biphenyls, i.e., Araclor 1254 (Fantel et al, 1979;Kitchin et al, 1981), but human liver preparations have also been used (Zhao et al, 1993). Other approaches to metabolism include pretreatment of gravidas with test agents followed by culture of exposed embryos after a suitable time period (Kochar, 1975;Beaudoin and Fisher, 1981) or preparation of culture medium from the serum of nonpregnant animals previously exposed to test compounds (Schmid et al, 1982).…”

Section: Preparation Of Liver Homogenates For Studies Of Biotransformmentioning

confidence: 99%

Rat Embryo Cultures for In Vitro Teratology

2000

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Mammalian embryos provide a particular challenge to those who wish to study developmental processes because development takes place inside the mother's body, thus limiting the investigator's ability to directly affect and observe the embryonic stages of development. Fortunately, as this unit illustrates, methods have been developed for in vitro culture of rodent embryos during early postimplantation (gestation days 9 to 11) and early fetal (gestation days 12 to 14) stages, which are the periods during which the major systems of the embryo are established. Embryos at these stages are particularly suitable for screening studies to determine the effects of teratological agents.

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A model combining the whole embryo culture with human liver S-9 fraction for human teratogenic prediction

Cited by 14 publications

References 18 publications

Toward better assessments of developmental toxicity using stem cell‐based in vitro embryogenesis models

Toward better assessments of developmental toxicity using stem cell‐based in vitro embryogenesis models

The Validation and Use of In Vitro Teratogenicity Tests

Rat Embryo Cultures for In Vitro Teratology

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