THE ROLE OF PROSTAGLANDIN PGE2 IN ENHANCING THE ENGRAFTMENT OF THE GENETICALLY MODIFIED HEMATOPOIETIC STEM CELLS

Gene therapy of hematological diseases, the basic principle of which is the transfer of a therapeutic gene into autologous hematopoietic stem cells (HSCs), is a possible option to cure potentially fatal genetic diseases in the last years. Nevertheless, there are still issues that need optimization or settlement. We investigated the effect of prostaglandin PGE2 in genetically modified mouse bone marrow cells and purified population of human hematopoietic stem cells (CD34 +) with lentiviral-GFP viral vector in order to improve gene transfer and promote implantation of genetically corrected cells. They were tested different conditions of incubation with PGE2 in primitive hematopoietic cells during transfection in order to identify the optimal condition that will yield high rates of gene transfer and implantation. It was observed superiority of expression in vivo in recipients who were treated with HSCs, transfected with GFP- lentiviral vector in presence of PGE2 during transfection, compared with the control group. In in vitro experiments was identified the condition in which cells were incubated with PGE2 immediately before the start of the transfection process as optimal on the rate of gene transfer, the number of viral copies per cell, and the GFP expression. Although is required additional research and confirmation of the results in vivo with the best incubation condition of HSCs with PGE2, these data contribute significantly to the effort of finding enhancing gene transfer methods in gene therapy of inherited diseases.ο