MDCK Cells

MDCK is another cell line that is widely utilized for permeability assessment. These cells differentiate into columnar epithelial cells and form tight junctions (like Caco-2 cells) when cultured on semi-permeable membranes. The use of MDCK cell line as a model to evaluate the intestinal transport characteristics of compounds was first discussed in 1989 (Cho et al., 1989). More recently, Irvine and colleagues (Irvine et al., 1999) investigated the use of MDCK cells as a tool for assessing the membrane permeability properties of early drug discovery compounds. MDCK cells were grown on transwell-COL membrane culture inserts at high density and cultured for 3 days. Apparent permeability values of 55 compounds with known human absorption values were determined in MDCK cell system. For comparison purposes, the permeability of the same compounds was also determined using Caco-2 cells. The authors reported that the permeability obtained with MDCK cells correlated equally well (as with permeability determined in Caco-2 cells) to human absorption. Given the fact that Caco-2 cells are derived from human colon carcinoma cells whereas the MDCK cells are derived from dog kidney cells, it is very likely that the expression level of various transporters may be grossly different in these two cell lines. Species difference should therefore be kept in mind before using MDCK cells as a primary screening tool for permeability in early drug discovery. One major advantage of MDCK cells over Caco-2 cells is the shorter cultivation period (3 days vs. 3 weeks). A shorter cell culture time becomes a significant advantage considering reduced labor and reduced down time in case of cell contamination.

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