The line was developed in 1977 by Jorgen Fogh at the Sloan-Kettering Institute for Cancer Research.[2] The research application of Caco-2 cells was developed during the 1980s by Alain Zweibaum group at INSERM, France as well as Ismael Hidalgo, at the Borchardt laboratory, University of Kansas and Tom Rauband at the Upjohn Company. The first publication of the discovery of the spontaneous enterocyte like differentiation was published by Alain Zweibaum group in 1983.[3]
Microscopically, Caco-2 cell cultures show obvious heterogeneity likely reflecting the complex mixture of cells found in the epithelial lining of the large and small intestine i.e. enterocytes, enteroendocrine cells, goblet cells, transit amplifying cells, paneth cells and intestinal stem cells.[5] Over time, the characteristics of the cells used in different laboratories have diverged, introducing inter-laboratory variation.[6] Despite such heterogeneity, Caco-2 cells are used in cell invasion studies, viral transfection research, and lipid transport.[7]
Caco-2 cells may be used as a confluent monolayer on a cell culture insert filter (e.g., Transwell). In this format, Caco-2 cells form a polarized epithelial cell monolayer that provides a physical and biochemical barrier to the passage of ions and small molecules.[4][8] The Caco-2 monolayer can be used as an in vitro model of the human small intestinal mucosa to predict the absorption of orally administered drugs. Kits, such as the CacoReady, have been developed to simplify this procedure.[9] A correlation between the in vitro apparent permeability across Caco-2 monolayers and the in vivo fraction absorbed has been reported.[10]Transwell diagram
^ abFogh, Jørgen; Fogh, Jens M.; Orfeo, Thomas (July 1977). "One Hundred and Twenty-Seven Cultured Human Tumor Cell Lines Producing Tumors in Nude Mice23". JNCI: Journal of the National Cancer Institute. 59 (1): 221–226. doi:10.1093/jnci/59.1.221. PMID327080.
^Sambuy Y, De Angelis I, Ranaldi G, Scarino ML, Stammati A, Zucco F (January 2005). "The Caco-2 cell line as a model of the intestinal barrier: influence of cell and culture-related factors on Caco-2 cell functional characteristics". Cell Biology and Toxicology. 21 (1): 1–26. doi:10.1007/s10565-005-0085-6. PMID15868485. S2CID125735.
^Vázquez-Sánchez MÁ. "CacoReady". Readycell. Readycell. Archived from the original on 2022-01-13. Retrieved 19 July 2018.
^Artursson P, Karlsson J (March 1991). "Correlation between oral drug absorption in humans and apparent drug permeability coefficients in human intestinal epithelial (Caco-2) cells". Biochemical and Biophysical Research Communications. 175 (3): 880–5. doi:10.1016/0006-291X(91)91647-U. PMID1673839.
Further reading
Artursson P, Palm K, Luthman K (March 2001). "Caco-2 monolayers in experimental and theoretical predictions of drug transport". Advanced Drug Delivery Reviews. 46 (1–3): 27–43. doi:10.1016/S0169-409X(00)00128-9. PMID11259831.
Shah P, Jogani V, Bagchi T, Misra A (2006). "Role of Caco-2 cell monolayers in prediction of intestinal drug absorption". Biotechnology Progress. 22 (1): 186–98. doi:10.1021/bp050208u. PMID16454510. S2CID37725450.