Near-infrared dye IR-780 alleviates hematopoietic system damage by promoting hematopoietic stem cells into quiescence

Abstract Worrying about potential radiation exposure is a general concern, but no effective pre-exposure radioprotective countermeasure is generally accepted1. Here, we found a small molecular near-infrared (NIR) dye IR-780, which promoted hematopoietic stem cells (HSCs) into quiescence to resist stress. When mice were treated with IR-780 before stress, increased HSC quiescence and better hematopoietic recovery were observed in IR-780-treated mice in stress conditions. However, when given after radiation, IR-780 did not show obvious benefit. Transplantation assay and colony-forming assay were carried out to determine self-renewal ability and repopulation capacity. Furthermore, IR-780 reduced the generation of reactive oxygen species (ROS) and DNA damage in HSCs after radiation. In homeostasis, the percentage of Lineage-, Sca-1 + , and c-Kit + cells (LSKs) and long-term HSCs (LT-HSCs) were improved, and more HSCs were in G0 state after administration of IR-780. Further investigations showed that IR-780 selectively accumulated in LT-HSCs with high mitochondria membrane potential (MMP) and entered cells by organic anion transporting polypeptides 1b2(Oatp1b2). Finally, IR-780 promoted human CD34 + hematopoietic stem cell reconstruction ability in NOD-Prkdc scid Il2rg null (NSG) mice after transplantation and improved repopulation capacity in vitro culture. Our research showed that IR-780 selectively entered MMP-high LT-HSCs and promoted them into dormancy, thus reducing hematopoietic injury and improving regeneration capacity. This novel approach might hold promise as a potential radiation countermeasure.