Human Caco-2 intestinal cell model

The Human Caco-2 Intestinal Cell Model A Valuable Tool for Studying Carotenoid... 

THE HUMAN CACO-2 INTESTINAL CELL MODEL A VALUABLE TOOL FOR STUDYING CAROTENOID ABSORPTION... 

The major absorption of tea catechins is the small intestine. EC, ECG, EGC, and EGCG were disposed at the intestinal epithelium by similar efflux and metabolism mechanisms. Intestinal epithelial membrane transport of catechins was studied via perfusion of EC and ECG in the human Caco-2 cell line. - The absorption and secretion transports of the four catechins, in the form of individual pure compounds, pure compound mixtures, and green tea extract, were studied in the human Caco-2 cell model. The results showed that the absorption transport of the four catechins in different doses was similar, but the green tea polyphenol mixtures could affect the secretion transport of individual catechins. It was suggested that the transporter competition may be responsible for the reduced efflux of EC, and metabolic competition may bring about a reduction in the formation of EGC sulfate and methylated EGC sulfate. ... 

G Wilson, IF Hassan, CJ Dix, I Williamson, R Shah, M Mackay. Transport and permeability properties of human Caco-2 cells An in vitro model of the intestinal epithelial cell barrier. J Controlled Release 11 25-40, 1990. 

There are a number of cell culture models available that mimic human epitheha in vivo (Caco-2, HT29, T84, lEC 18, TC7, LLCPKl, MDCK). Some of these cells are derived from human colon carcinomas (e.g., Caco-2, T84, HT29) and have many properties of the normal intestinal epithelium. The Caco-2 cell model is one of the... 

The human Caco-2 cell line has been shown to be of limited value as an in vitro model for the absorption and enzymatic cleavage of ester prodrugs in the gut wall mucosa because the expression pattern of CES1 and CES2 resembles more closely to the liver rather than the intestine [107]. 

PAMPA-biomimetic-Caco-2-comparison Several in vitro assays have been developed to evaluate the Gl absorption of compounds. Our aim was to compare three of these methods (/) the BAMPA method, which offers a HT, noncellular approach to the measurement of passive transport ( ) the traditional Caco-2 cell assay, the use of which as a HT tool is limited by the long cell differentiation time (21 days) and (// ) The BioCoat HTS Caco-2 assay system, which reduces Caco-2 cell differentiation to three days. The transport of known compounds (such as cephalexin, propranolol, or chlorothiazide) was studied at pH 7.4 and 6.5 in BAMPA and both Caco-2 cell models. Permeability data obtained was correlated to known values of human absorption. Best correlations (f= 0.9) were obtained at pH 6.5 for BAMPA and at pH 7.4 for the Caco-2 cells grown for 21 days. The Caco-2 BioCoat HTS Caco-2 assay system does not seem to be adequate for the prediction of absorption. The overall results indicate that BAMPA and the 21 -day Caco-2 system can be complementary for an accurate prediction of human intestinal absorption. 

In-vitro models can provide preliminary insights into some pharmacodynamic aspects. For example, cultured Caco 2 cell lines (derived from a human colorectal carcinoma) may be used to simulate intestinal absorption behaviour, while cultured hepatic cell lines are available for metabolic studies. However, a comprehensive understanding of the pharmacokinetic effects vfill require the use of in-vivo animal studies, where the drug levels in various tissues can be measured after different dosages and time intervals. Radioactively labelled drugs (carbon-14) may be used to facilitate detection. Animal model studies of human biopharmaceutical products may be compromised by immune responses that would not be expected when actually treating human subjects. 

The Caco-2 cell line was isolated from a human colon carcinoma, and has been characterized as one of the best in vitro models of intestinal epithelium. Indeed, in contrast to other intestinal cell lines, Caco-2 cells are able to constitute a homogenous monolayer and to spontaneously differentiate into polarized cells, highly similar to human mature enterocytes, after approximately 2 weeks of culture. Furthermore, the Caco-2 cells present microvillosities at the apical side and have a high transmembrane resistivity, which confirms the fact that the cells are confluent and link to one another via gap junctions. Finally, they can absorb different compounds, express many enzymes involved in intestinal metabolic pathways (Pinto et al. 1983, Musto et al. 1995, Salvini et al. 2002), and give reproducible in vitro results consistent with results obtained in in vivo studies (Artursson and Karlsson 1991). 

Ferruzzi, M. G. et al. (2001). Assessment of degradation and intestinal cell uptake of carotenoids and chlorophyll derivatives from spinach puree using an in vitro digestion and Caco-2 human cell model. J. Agric. Food Chem. 49(4) 2082-2089. 

The enthusiasm for using Caco-2 cells and other epithelial cell cultures in studies of drug transport processes has been explained by the ease with which new information can be derived from these fairly simple in vitro models [7]. For instance, drug transport studies in Caco-2 cells grown on permeable supports are easy to perform under controlled conditions. This makes it possible to extract information about specific transport processes that would be difficult to obtain in more complex models such as those based on whole tissues from experimental animals. Much of our knowledge about active and passive transport mechanisms in epithelia has therefore been obtained from Caco-2 cells and other epithelial cell cultures [10-15]. This has been possible since Caco-2 cells are unusually well differentiated. In many respects they are therefore functionally similar to the human small intestinal enterocyte, despite the fact that they originate from a human colorectal carcinoma [16, 17]. 

Borchardt. Characterization of the human colon carcinoma cell line (Caco-2) as a model system for intestinal epithelial permeability, Gastroenterology 1989, 96, 736—749... 

Brodin, S. Frokjaer, M. Taub, and B. Steffansen. Dipeptide model prodrugs for the intestinal oligopeptide transporter. Affinity for and transport via hPepTl in the human intestinal Caco-2 cell line.,... 

The main reasons for the popularity of the Caco-2 cell line are that the cells are easy to maintain in culture, and they develop unusually high degree of differentiation spontaneously under standard culture conditions. In fact, Caco-2 is the only human intestinal cell line that has been found so far spontaneously to undergo functional enterocytic differentiation. The cells exhibit a good reproducibility, robustness and functional properties of human intestinal epithelial cells. The model has proved capable of predicting the oral absorption of a variety of drug compounds [see references in 10]. 

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