RESUMEN
OBJECTIVES: ß-thalassemia and sickle cell disease are hemoglobinopathies with reduced/absent ß chains in the former and dysfunctional ß chains in the latter. In both conditions, up-regulation of hemoglobin F through demethylation can alleviate the symptoms. This can be attained with drugs such as thalidomide and sodium butyrate. MATERIALS AND METHODS: This study was performed on erythroid progenitors derived from CD133+ cord blood stem cells. Erythroid progenitors were treated with thalidomide and sodium butyrate in single and combined groups. Colony-formation potential in each group was evaluated by the colony assay. Real-time polymerase chain reaction (RT-PCR) was used to evaluate the effect of these drugs on histone H3 lysine 27 (H3K27) methylation patterns. FINDINGS: Compared to other treatment groups, CD133+ cells treated with thalidomide alone produced more hematopoietic colonies. Thalidomide alone was also more effective in decreasing H3K27 methylation. CONCLUSIONS: Thalidomide shows superiority to sodium butyrate as a hypomethylating agent in this cell culture study, and it has the potential to become conventional treatment for sickle cell disease and ß-thalassemia.
Asunto(s)
Antígenos CD , Butiratos/farmacología , Células Precursoras Eritroides/metabolismo , Glicoproteínas , Histonas/metabolismo , Péptidos , Teratógenos/farmacología , Talidomida/farmacología , Antígeno AC133 , Anemia de Células Falciformes/tratamiento farmacológico , Anemia de Células Falciformes/metabolismo , Células Cultivadas , Sangre Fetal , Hemoglobina Fetal/biosíntesis , Humanos , Metilación/efectos de los fármacos , Reacción en Cadena en Tiempo Real de la Polimerasa , Regulación hacia Arriba/efectos de los fármacos , Talasemia beta/tratamiento farmacológico , Talasemia beta/metabolismoRESUMEN
Umbilical cord Blood (UCB) as a source of Hematopoietic Stem/Progenitor cells (HSPCs) used for Umbilical cord blood transplantation (UCBT). The main obstacle in application of this source as an appropriate source of HSPCs is low volume of this product. So ex vivo expansion of these cells in a microenvironment which mimic body condition is important. In current study we designed biocompatible microwells in which collagene type I is coated by softlitography method. Our findings designated that in 3-Dimensional (3D) microenvironment CD133(+) UCB derived HSC expanded significantly compared to 2-Dimensional (2D) microenvironment.