Submitted to: Book Chapter
Publication Type: Book / Chapter
Publication Acceptance Date: 1/16/2009
Publication Date: 3/22/2009
Citation: Glahn, R.P. 2009. The use of caco-2 cells in defining nutrient bioavailability: application to iron bioavailability of foods. In: McClements, D., Decker, E. Designing functional foods: measuring and controlling food structure breakdown and nutrient absorption. Cambridge, UK: Woodhead Publishing Limited. p. 340-361. Interpretive Summary:
Technical Abstract: In vitro models can be a useful and productive approach in many if not all of the life sciences. Furthermore, coupling in vitro studies with in vivo testing can be even more productive as in vitro studies are by nature less expensive, rapid, and often allow greater manipulation and simplification for mechanistic studies of physiological processes at the level of the cell. These cellular observations often give clues to in vivo effects and thus allow researchers to design more definitive animal and human trials. However, as with any in vitro model, care must be taken to accurately reproduce the physiological conditions relevant to the experimental objectives; otherwise, one runs the risk of generating information that is merely an artifact of the conditions, and not representative of the in vivo physiology it was designed to replicate. For studies of intestinal absorption of nutrients, the use of intestinal cell cultures, has facilitated our understanding of the mechanisms of absorption of many nutrients. Of the major cell lines used in nutrition research, the Caco-2 cell line has become the widely used and characterized for a broad range of nutrient uptake studies. In most cases, the use of Caco-2 cell monolayers has proven useful for elucidating mechanisms of nutrient uptake; however, Caco-2 cell monolayers may not always be useful, necessary or appropriate as a tool to predict bioavailability of nutrients. This is because the Caco-2 cell monolayer is merely a layer of cells, and there are a multitude of other factors that can regulate and influence absorption in the intestinal lumen. Not all of these factors such as the intestinal microflora, nutritional status, disease states, nutrient interactions, etc. can be replicated in vitro. There are definite limitations for intestinal cell monolayers and these should always be considered for each nutrient of study. As stated previously, there is a multitude of literature demonstrating that this cell line is useful in defining mechanisms of uptake of various nutrients. Hence this chapter will focus on an example of the next level of use for cell culture models, which is the use of the cell line as a high throughput screening tool for food iron bioavailability. Iron represents a unique challenge in nutrition as it is an essential nutrient but often poor in bioavailability and thus Fe deficiency affects more than a third of the world’s population. Given the complexity of iron bioavailability in foods, the use of an in vitro model is particularly essential for developing foods with more bioavailable Fe.