The Relationship Between Oxygen Concentration, Reactive Oxygen Species and the Biological Characteristics of Human Bone Marrow Hematopoietic Stem Cells

Abstract

Peripheral hematopoietic stem cells (HSCs) are exposed to environments with significantly different oxygen concentrations than those of bone marrow (BM) when they are expanded under normal oxygen conditions in vitro before transplantation. Therefore, we asked whether the biological properties of HSCs change. In this study, we simulated the oxygen environment experienced by peripheral blood stem cells (PBSCs) during peripheral blood stem cell transplantation (PBSCT) to study the effects of oxygen concentration and reactive oxygen species on their biological characteristics. We further analyzed the relationship between oxygen concentrations, reactive oxygen species (ROS) and biological characteristics of mouse HSCs. Our analysis focused on the detection of ROS, in vitro amplification, directional differentiation, cell apoptosis, cell cycle, migration, and the detection of colony-forming unit–spleen (CFU-S) from non-obese diabetic (NOD)/sevete combined immunodeficient (SCID) mice irradiated with a sublethal dose of γ-radiation. We determined that lower than normal, oxygen concentrations in hypoxic environment, reduced ROS generation, induced expansion of more primitive CD34 +AC133 +HSCs and active CD34 + HSCs, maintaining more stem cells in the G 0/G 1 phase, which is helpful for the growth of pre-colony forming unit (pre-CFUs) and various colonies (BFU-E, CFU-GM, CFU-GEMM). At the same time, a hypoxic environment maintained the migratory ability of HSCs, which significantly promotes the growth of CFU-S after transplantation of HSCs into irradiated NOD/SCID mice. BM HSCs exposed to normal or to inconsistent, highly variable oxygen concentrations produce high levels of ROS; in these instances, the above features and functional indicators were relatively low. Our results showed that the ROS levels of BM HSCs in PBSCT were closely related to the oxygen concentration surrounding the cells (and to its stability). High oxygen concentrations lead to high levels of ROS, which were not helpful to maintain the biological characteristics of BM HSCs.