A lipophilic iron chelator can replace transferrin as a stimulator of cell proliferation and differentiation.

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Abstract
Of the different growth supplements used in chemically defined media, only transferrin is required for differentiation of tubules in the embryonic mouse metanephros. Since transferrin is an Fe-carrying protein, the crucial role of Fe for tubulogenesis was determined. Differentiation of metanephric tubules in whole embryonic kidneys and in a transfilter system was studied. The tissues were grown in chemically defined media containing transferrin, apotransferrin, the metal-chelator complex ferric pyridoxal isonicotinoyl hydrazone (FePIH) and excesses of Fe3+. Although apotransferrin was not as effective as Fe-loaded transferrin in promoting proliferation in the differentiating kidneys, excess Fe3+ at up to 100 .mu.M, 5 times the normal serum concentration, could not promote differentiation or proliferation. Fe coupled to the nonphysiological, lipophilic iron chelator, pyridoxal isonicotinoyl hydrazone, to form FePIH, could sustain levels of cell proliferation and tubulogenesis similar to those attained by transferrin. The role of transferrin in cell proliferation during tubulogenesis is solely to provide Fe. Since FePIH apparently bypasses the receptor-mediated route of Fe intkae, the use of FePIH as a tool for investigating cell proliferation and its regulation is suggested.