Effect of CDDO-me on Myelopoiesis in Naive Mice and Mice Undergoing Bone Marrow Transplantation (BMT)
AdvisorMurphy, William J
Cell and Molecular Biology
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ABSTRACT To treat cancer and other hematological diseases, large numbers of hematopoietic stem cells (HSC) and hematopoietic progenitor cells (HPC) are needed. The objectives of this study were to examine the toxicity effect of the synthetic triterpenoid CDDO-me in vivo, to investigate the effect of CDDO-me on myeloid expansion and mobilization, to determine the hematopoietic growth factor production in the serum of mice that received CDDO-me, and to look at the effect of CDDO-me on immune system recovery after bone marrow transplantation (BMT). Our findings show that CDDO-me at 240 ug/dose BID is a lethal dose for C57BL/6 female mice. In contrast, CDDO-me at 120 ug/dose BID was well tolerated in pre-BMT, but lethal in pre- and post-BMT and in post-BMT. CDDO-me at 60 ug/dose BID was well tolerated in pre- and/ or post-BMT in a murine model. We also found that treatment with CDDO-me (120 ug/ dose, BID) significantly increased myeloid, erythroid, and CFU-HPPs in the spleen and the bone marrow. In addition to inducing CFU-GM expansion, treatment with CDDO-me caused a significant increase in myeloid and erythroid progenitors in the spleen and blood. The level of G-CSF in the serum was significantly increased by CDDO-me treatment. Moreover, a significant increase in spleen CFU-GM in the mice that received CDDO-me (60 ug/dose BID) at day 14 post-BMT was observed. From these results we concluded that: treatment with CDDO-me (120 ug/dose BID) enhanced myelopoiesis and caused mobilization of myeloid and myeloid progenitor cells into the spleen and blood. CDDO-me (60 ug/dose BID) had a positive effect on myeloid and myeloid progenitor cell recovery at day 14 post-BMT. Finally, the level of G-CSF in the serum was significantly increased after CDDO-me treatment.