Protective Effect of the c-mpl Agonist Romiplostim on Megakaryocytopoiesis of Human CD34+Hematopoietic Progenitor Cells Exposed to Ionizing Radiation

Abstract

A thrombopoiesis-stimulating protein, the myeloproliferative leukemia virus protooncogene (Mpl) ligand romiplostim (RP), is currently approved as a therapeutic agent for idiopathic thrombocytopenic purpura in many countries. Although the action of the initial MPL ligand thrombopoietin (TPO) on human megakaryocytic regeneration from irradiated human hematopoietic stem cells has been examined, there are few reports on the action of RP. In the present study, freshly prepared nonirradiated and 2-Gy X-irradiated human CD34 positive (CD34+) cells from placental umbilical cord blood were cultured with a combination of RP and various cytokines. As a result, the effect of RP on cell proliferation of nonirradiated CD34+ cells was found to be comparable to that of TPO. However, the stimulating activity of RP on megakaryocytic progenitor-derived colony formation was markedly lower compared with TPO. Regarding the action of RP with various cytokines, the present results showed that a combination of RP with interleukin-3 (IL-3) or IL-3 plus stem cell factor (SCF) showed a high regenerative effect on cell proliferation, megakaryopoiesis, thrombopoiesis, and megakaryocyte colony formation from X-irradiated CD34+ cells. The present study showed that human recombinant RP has potential effects on human megakaryocytic regeneration from X-irradiated human CD34+ cells and synergistically acts with IL-3 and IL-3 plus SCF, just as observed with TPO.