Retinyl acetate and all‐trans‐retinoic acid enhance erythroid colony formation in vitro by circulating human progenitors in an improved serum‐free medium

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Abstract
Retinyl acetate (RA) dramatically increased the production of early (d16) erythroid colonies in vitro by circulating human progenitor cells growing in an improved serum-free (SF) medium. In the absence of either erythropoietin (Epo) or insulin-like growth factor I (IGF-I), RA alone was able to induce the hemoglobinization of cells in these erythroid colonies. RA synergized with Epo or with IGF-I to yield increased numbers of well-hemoglobinized early colonies. In the presence of defined burst promoting activity (BPA) provided by recombinant human interleukin 3 (rHuIL-3) and hemin, RA and all-trans-retinoic acid (ATRA) were identical with respect to their differentiation-inducing function for early erythroid colonies. ATRA increased the number of these colonies in a concentration-dependent manner, with maximal stimulation (3.5-fold) occurring at 30 nM in the presence of 5.5 ng/ml IL-3,0.1 mM hemin, 3.0 U/ml Epo and 30 nM IGF-I. This appears to be the first demonstration of erythropoietic activity of two metabolic derivatives of vitamin A in SF medium.