Abstract: The present invention is directed to compositions comprising heme-containing components and to methods that stimulate erythropoiesis comprising administration of a composition of the invention, such as purified hemoglobin. Surprisingly, heme-containing components such as hemoglobin can induce erythropoiesis in the presence of decreased concentrations of erythropoietin (Epo) and, in fact, functions synergistically with Epo. Further, heme-containing components can be used alone or in conjunction with Epo for the treatment of anemias and other disorders due to decreases in erythropoietin or iron. It has been discovered that, in the presence of Epo, both hemoglobin and cross-linked hemoglobin can compensate for the reduction in erythroid cell growth and differentiation that occurs in the presence of reduced concentrations of Epo. The effect is specific to erythropoiesis, as evidenced by a lack of growth of non-erythroid progenitors such as CFU-GM.

Abstract: The present invention describes a serum-free medium that promotes the growth and differentiation of erythroid cells, cells that are highly transducible by a non-viral method and genes which increase the growth of erythroid cells and decrease their dependency on Epo. This invention can be used in the expansion of hematopoietic stem cells to produce cultures of erythroid cells as a source of erythroid-specific proteins such as hemoglobin. Hematopoietic stem cells are cultured ex vivo in a serum-free culture medium with the addition of IL-3, SCF and EPO. Cells transfected with the gene described in the present invention can be cultured in the serum-free culture medium with decreased dependency on Epo and other cytokines, thereby reducing the cost of the production of hemoglobin.