Human Skin Models for Research Applications in Pharmacology and Toxicology: Introducing NativeSkin<sup>®</sup>, the “Missing Link” Bridging Cell Culture and/or Reconstructed Skin Models and Human Clinical Testing

WeverBart, De; KurdykowskiSandrine,; DescarguesPascal,

doi:10.1089/aivt.2014.0010

Cited by 44 publications

(49 citation statements)

References 18 publications

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“…vi) Kinetics can be directly measured without dilution in tissue fluids or organs. vii) Removal of ethical costs by avoidance of animal experiments (as applies to the Cosmetics Regulation in the EU) (De Wever et al, 2015).…”

Section: General Introductionmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

123

103

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SummaryModels of the outer epithelia of the human body -namely the skin, the intestine and the lung -have found valid applications in both research and industrial settings as attractive alternatives to animal testing. A variety of approaches to model these barriers are currently employed in such fields, ranging from the utilization of ex vivo tissue to reconstructed in vitro models, and further to chip-based technologies, synthetic membrane systems and, of increasing current interest, in silico modeling approaches. An international group of experts in the field of epithelial barriers was convened from academia, industry and regulatory bodies to present both the current state of the art of non-animal models of the skin, intestinal and pulmonary barriers in their various fields of application, and to discuss research-based, industry-driven and regulatory-relevant future directions for both the development of new models and the refinement of existing test methods. Issues of model relevance and preference, validation and standardization, acceptance, and the need for simplicity versus complexity were focal themes of the discussions. The outcomes of workshop presentations and discussions, in relation to both current status and future directions in the utilization and development of epithelial barrier models, are presented by the attending experts in the current report.

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Section: General Introductionmentioning

confidence: 99%

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Gordon

Daneshian

Bouwstra

et al. 2015

ALTEX

123

103

View full text Add to dashboard Cite

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“…Different cell types, ranging from immortalized cell lines to primary cells, were selected to recapitulate relevant key parameters. As an example, the response to topical remedies of NativeSkin skin explants—originating from full‐thickness skin biopsies—has been shown to reproduce that of human skin, enabling its use as a predictive model to test preclinical dermatocosmetic products . Several skin models hold promise for drug screening, as they have been shown to develop inflammatory phenotypes when dosed with artificial cytokines, or when cocultivated with immune cells or bacterial pathogens …”

Section: Transferable In Vitro Organ Modelsmentioning

confidence: 99%

Integrated Microphysiological Systems: Transferable Organ Models and Recirculating Flow

et al. 2019

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Advanced 3D in vitro models (organoids or tissue cultures) may constitute an alternative test system for initial screening and characterization of lead compounds in early development stages. 3D tissue structures have been proven to more closely reproduce behavior and characteristics of a living organism in comparison to traditional 2D cell cultures in dishes. [3,4] For such advanced in vitro models, a large range of automated test systems and analysis methods would be potentially available, so that testing procedures could be parallelized to increase throughput. This prospect has fueled rapid progress in developing 3D in vitro models of individual organs of the human body for pharmaceutical and toxicological research. Such model systems need to be carefully engineered to faithfully reproduce physiological effects, pharmacokinetics, and toxicity that may occur within a human body in order to enable successful identification of new drug compounds and the corresponding mechanisms of action.To realize advanced in vitro models, not only the 3D nature of a human body and its tissues needs to be considered, but also the potential interplay of organs. More recently, microphysiological systems (MPSs) emerged in an effort to better recapitulate in vivo conditions of human physiology and to better control in vitro cell and tissue culturing conditions. [5][6][7][8][9][10] MPSs are in vitro platforms designed to model the spatial, chemical, structural, and physiological elements of in vivo cellular environments and include, in most cases, a combination of advanced cell-culture or tissue models and microfluidic technology. Important features of MPSs include the use of more complex multicellular or tissue structures and the possibility to expose cells to cues that they also experience in their native environment in the human body, such as mechanical cues in the form of flow-induced shear stress, [11,12] stretching, [13,14] or biochemical stimuli. [15][16][17] Key features of MPSs that are usually combined in a single system include: a) advanced 3D tissue or organ models, b) the presence of culture medium flow or perfusion, and c) fluidic interconnection and potential interaction of different organ models through the liquid phase: a) 3D tissue models feature increased functionality and a more organotypic cellular microenvironment in comparison to Studying and understanding of tissue and disease mechanisms largely depend on the availability of suitable and representative biological model systems. These model systems should be carefully engineered and faithfully reproduce the biological system of interest to understand physiological effects, pharmacokinetics, and toxicity to better identify new drug compounds. By relying on microfluidics, microphysiological systems (MPSs) enable the precise control of culturing conditions and connections of advanced in vitro 3D organ models that better reproduce in vivo environments. This review focuses on transferable in vitro organ models and integrated MPSs that host these transferable biologic...

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“…The closest experimental approach under which to study metabolism in skin to compare to in vivo situations, is to use viable ex vivo human skin in culture (Manevski et al, 2015;Zalko et al, 2011). Effectively a living system, the various compartments (both inter and intra cellular) remain relatively intact and tissue viability as well as the levels of some biomarkers are preserved for several days (de Wever et al, 2015;Varani et al, 2007). Several studies have used the incubation of whole skin in media containing concentrations of chemical substrate to study activity rates (Eilstein et al, 2014;Manevski et al, 2015), while topical application of the substrate on cultured skin explants or models is favoured in studies covering both skin penetration of the test substrate and identification of its major metabolites (Jacques et al, 2014).…”

Section: Accepted Manuscriptmentioning

confidence: 99%

A study of inter-individual variability in the Phase II metabolism of xenobiotics in human skin

et al. 2018

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Understanding skin metabolism is key to improve in vitro to in vivo extrapolations used to inform risk assessments of topically applied products. However, published literature is scarce and usually covers a limited and non-representative number of donors. We developed a protocol to handle and store ex vivo skin samples post-surgery and prepare skin S9 fractions to measure the metabolic activity of Phase II enzymes. Preincubation of an excess of cofactors at 37 °C for fifteen minutes in the S9 before introduction of the testing probe, greatly increased the stability of the enzymes. Using this standardised assay, the rates of sulphation (SULT) and glucuronidation (UGT) of 7-hydroxycoumarin, methylation (COMT) of dopamine and N-acetylation (NAT) of procainamide were measured in the ng/mg protein/h (converted to ng/cm/h) range in eighty-seven individuals. Glutathione conjugation (GST) of 1-chloro-2,4-dinitrobenzene was assessed in a smaller pool of fifty donors; the metabolic rate was much faster and measured over six minutes using a different methodology to express rates in μg/mg protein/min (converted to μg/cm/min). A comprehensive statistical analysis of these results was carried out, separating donors by age, gender and metabolic rate measured.

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Human Skin Models for Research Applications in Pharmacology and Toxicology: Introducing NativeSkin^®, the “Missing Link” Bridging Cell Culture and/or Reconstructed Skin Models and Human Clinical Testing

Cited by 44 publications

References 18 publications

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Integrated Microphysiological Systems: Transferable Organ Models and Recirculating Flow

A study of inter-individual variability in the Phase II metabolism of xenobiotics in human skin

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Human Skin Models for Research Applications in Pharmacology and Toxicology: Introducing NativeSkin®, the “Missing Link” Bridging Cell Culture and/or Reconstructed Skin Models and Human Clinical Testing

Cited by 44 publications

References 18 publications

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Non-animal models of epithelial barriers (skin, intestine and lung) in research, industrial applications and regulatory toxicology

Integrated Microphysiological Systems: Transferable Organ Models and Recirculating Flow

A study of inter-individual variability in the Phase II metabolism of xenobiotics in human skin

Contact Info

Product

Resources

About

Human Skin Models for Research Applications in Pharmacology and Toxicology: Introducing NativeSkin^®, the “Missing Link” Bridging Cell Culture and/or Reconstructed Skin Models and Human Clinical Testing