Przybylla, R.; Krohn, M.; Sellin, M.-L.; Frank, M.; Oswald, S.; Linnebacher, M. Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine. Cells2023, 12, 2371.
Przybylla, R.; Krohn, M.; Sellin, M.-L.; Frank, M.; Oswald, S.; Linnebacher, M. Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine. Cells 2023, 12, 2371.
Przybylla, R.; Krohn, M.; Sellin, M.-L.; Frank, M.; Oswald, S.; Linnebacher, M. Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine. Cells2023, 12, 2371.
Przybylla, R.; Krohn, M.; Sellin, M.-L.; Frank, M.; Oswald, S.; Linnebacher, M. Novel In Vitro Models for Cell Differentiation and Drug Transport Studies of the Human Intestine. Cells 2023, 12, 2371.
Abstract
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.
Keywords
ADME; drug transport; jejunum; small intestine; differentiation; 2D cell culture
Subject
Medicine and Pharmacology, Pharmacology and Toxicology
Copyright:
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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