Abstract
Alternative functional in vitro models of human intestinal epithelia
Frontiers in pharmacology, v 4, pp 79-79
01 Jan 2013
PMID: 23847534
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
Physiologically relevant sources of absorptive intestinal epithelial cells are crucial for human drug transport studies. Human adenocarcinoma-derived intestinal cell lines, such as Caco-2, offer conveniences of easy culture maintenance and scalability, but do not fully recapitulate
in vivo
intestinal phenotypes. Additional sources of renewable physiologically relevant human intestinal cells would provide a much needed tool for drug discovery and intestinal physiology. We compared two alternative sources of human intestinal cells, commercially available primary human intestinal epithelial cells (hInEpCs) and induced pluripotent stem cell (iPSC)-derived intestinal cells to Caco-2, for use in
in vitro
transwell monolayer intestinal transport assays. To achieve this for iPSC-derived cells, intestinal organogenesis was adapted to transwell differentiation. Intestinal cells were assessed by marker expression through immunocytochemical and mRNA expression analyses, monolayer integrity through Transepithelial Electrical Resistance (TEER) measurements and molecule permeability, and functionality by taking advantage the well-characterized intestinal transport mechanisms. In most cases, marker expression for primary hInEpCs and iPSC-derived cells appeared to be as good as or better than Caco-2. Furthermore, transwell monolayers exhibited high TEER with low permeability. Primary hInEpCs showed molecule efflux indicative of P-glycoprotein (Pgp) transport. Primary hInEpCs and iPSC-derived cells also showed neonatal Fc receptor-dependent binding of immunoglobulin G variants. Primary hInEpCs and iPSC-derived intestinal cells exhibit expected marker expression and demonstrate basic functional monolayer formation, similar to or better than Caco-2. These cells could offer an alternative source of human intestinal cells for understanding normal intestinal epithelial physiology and drug transport.
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Details
- Title
- Alternative functional in vitro models of human intestinal epithelia
- Creators
- Amanda L. Kauffman - Johnson & JohnsonAlexandra V. Gyurdieva - Johnson & JohnsonJohn R. Mabus - Johnson & JohnsonChrissa Ferguson - Johnson & JohnsonZhengyin Yan - Johnson & JohnsonPamela J. Hornby - Johnson & Johnson
- Publication Details
- Frontiers in pharmacology, v 4, pp 79-79
- Publisher
- Frontiers Media S.A
- Resource Type
- Abstract
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000347011700078
- Scopus ID
- 2-s2.0-84881588296
- Other Identifier
- 991021931909604721
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- Web of Science research areas
- Pharmacology & Pharmacy