NEAR-INFRARED DYE IR-780 ALLEVIATES HEMATOPOIETIC SYSTEM DAMAGE BY PROMOTING HEMATOPOIETIC STEM CELLS INTO QUIESCENCE

Abstract

ABSTRACT Potential radiation exposure is a general concern, but there still lacks radioprotective countermeasures. Here, we found a small molecular near-infrared 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 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 of HSCs. Furthermore, IR-780 pretreatment 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 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 mitochondria membrane potential high LT-HSCs (MMP-high LT-HSCs). Finally, IR-780 promoted human CD34+ HSC reconstruction ability in NOD-PrkdcscidIl2rgnull 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 countermeasure for radiation injury.