Ferumoxytol promotes haematopoietic stem cell post-injury regeneration as a reactive oxygen species scavenger

Abstract

Under stress conditions, such as ex vivo culture, chemotherapy, irradiation and infection, haematopoietic stem cells (HSCs) actively divide to maintain blood cell production. This process leads to production of reactive oxygen species (ROS) that causes HSC exhaustion and haematopoietic failure. Here we show that ferumoxytol (FMT; Feraheme), a Food and Drug Administration-approved nanodrug, is a powerful ROS scavenger capable of relieving ROS in stressed HSCs, facilitating their post-injury regeneration. Mechanistically, the catalase-like activity of FMT reduces intracellular levels of H₂O₂ and diminishes H₂O₂-induced cytotoxicity. Moreover, FMT maintains long-term regenerative capacity of transplanted HSCs in pre-conditioned leukaemic mice and shows potential to effectively eliminate leukaemia in vivo while preserving HSCs. Our study highlights FMT as a powerful clinical tool to promote haematopoietic cell recovery in patients undergoing stress-generating treatments.