MILK-DERIVED GROWTH-FACTORS AS SERUM SUPPLEMENTS FOR THE GROWTH OF FIBROBLAST AND EPITHELIAL-CELLS

We have investigated the response of several epithelial and fibroblast ic cells to a mitogenic extract of bovine milk. Cation exchange chroma tography was used to produce a mitogen-rich fraction from an industria l whey source that, although comprising only 0.5% of total whey protei n, contained the bulk of the growth factor activity. This fraction was a source of potent growth promoting activity for all mesodermal-deriv ed cells tested, including human skin and embryonic lung fibroblasts, Balb/c 3T3 fibroblasts, and rat L6 myoblasts. Maximal growth of all th ese cell types exceeded that observed in 10% fetal bovine serum. Felin e kidney and baby hamster fibroblasts and Chinese hamster ovary cells were less responsive, achieving a maximal growth response of 50-75% th at observed in 10% fetal bovine serum. Maximal growth achieved in whey -extract-supplemented cultures of Balb/c 3T3 and human skin fibroblast s, and L6 myoblast cultures exceeded that seen in response to recombin ant acidic or basic fibroblast growth factor, platelet-derived growth factor, insulin-like growth factor, or epidermal growth factor. Import antly, addition of low concentrations of fetal bovine serum to the whe y-derived mitogenic fraction produced an additive response. However. c oncentrated milk-derived factors were found to be inhibitory to the gr owth of all epithelial lines tested, including rat intestinal epitheli al cells, canine kidney epithelial cells, and mink lung cells. It is c oncluded that industrial whey extracted in this form constitutes an im portant source of potent growth-promoting agents for the supplementati on of mesodermal-derived cell cultures.