Intestinal Epithelium and Drug Transporters

Ménochet, Karelle; Chanteux, Hugues; Henshall, Jamie; Nicolas, Jean‐Marie; Wright, Sarah; Asperen, Judith van; Ungell, Anna‐Lena

doi:10.1002/9781119772729.ch3

Cited by 2 publications

(1 citation statement)

References 248 publications

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“…Several uptake (solute carrier transporters; SLCs) and ATP-binding cassette (ABC) efflux transporters are located in the apical membrane of enterocytes. SLCs facilitate drug absorption and are the most abundant transporters in the small intestine [9], while ABC transporters limit intestinal absorption and promote the excretion of endogenous substances [10]. In addition, NRs function as modulators of drug-metabolizing enzymes and DT expression [11].…”

Section: Introductionmentioning

confidence: 99%

Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine

Przybylla,

Krohn,

Sellin

et al. 2023

Cells

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The most common in vitro model for absorption, distribution, metabolism, and excretion (ADME) purposes is currently the Caco-2 cell line. However, clear differences in gene and protein expression towards the small intestine and an, at best, fair prediction accuracy of intestinal drug absorption restrict the usefulness of a model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screening of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier-forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, anda higher degree of differentiation was observed in 5/10 cell lines. All lines expressed multiple transporter molecules, with the expression levels in three lines being close to those of small intestinal epithelial cells. Compared with the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In summary, these lines would be better-suited human small intestinal epithelium models for basic and translational research, especially for ADME studies.

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Section: Introductionmentioning

confidence: 99%

Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine

Przybylla,

Krohn,

Sellin

et al. 2023

Cells

View full text Add to dashboard Cite

show abstract

Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine

Przybylla,

Krohn,

Sellin

et al. 2023

Preprint

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Still, the most common in vitro model for absorption, distribution, metabolism and excretion (ADME) purposes is the Caco-2 cell line. However, clear differences in gene- and protein expression towards the small intestine and an at best fair prediction accuracy of intestinal drug absorption restrict the usefulness as model for intestinal epithelial cells. To overcome these limitations, we evaluated a panel of low-passaged patient-derived colorectal cancer cell lines of the HROC collection concerning similarities to small intestinal epithelial cells and their potential to predict intestinal drug absorption. After initial screen of a larger panel, ten cell lines with confluent outgrowth and long-lasting barrier forming potential were further characterized in close detail. Tight junctional complexes and microvilli structures were detected in all lines, differentiated epithelial cells were abundant in 7/10. All lines expressed multiple transporter molecules, with expression levels in three lines being close to those of small intestinal epithelial cells. Compared to the Caco-2 model, three HROC lines demonstrated both higher similarity to jejunal epithelial tissue cells and higher regulatory potential of relevant drug transporters. In sum, these lines would be better suited human small intestinal epithelium models for basic and translational research; especially for ADME studies.

show abstract

Intestinal Epithelium and Drug Transporters

Cited by 2 publications

References 248 publications

Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine

Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine

Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine

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