In vitro Induction of Fetal Hemoglobin in Erythroid Cells Derived from CD133 Cells by Transforming Growth Factor-b and Stem Cell Factor

Increased fetal hemoglobin (HbF) in b-globin gene disorders ameliorates the clinical symptoms of the underlying disease. 5-azacytidine, butyrate and hydroxyurea, have been shown to activate g-globin gene expression. It has also been found that hematopoietic growth factors can influence expression of g-globin in erythroid cultures and in animal models. This study was designed to evaluate the in vitro effects of the stem cell factor (SCF) and transforming growth factor-b (TGF-b) on g-globin gene reactivation of erythroid precursors derived from CD133+ cells in vitro. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) analysis showed increased expression of the g-globin transcript in cell culture groups containing either TGF- b or SCF or both as compared to control (2.2-, 2.7- and 5.5-fold, respectively) (p<0.01). Production of HbF in a differentiated population was demonstrated using flow cytometry. The results of this study suggest that SCF and TGF-b warrant further evaluation as potential therapeutic drugs for the treatment of b-globin gene disorders.