Altered stem cell properties of human hematopoietic stem and progenitor cells based on bone region location

Abstract The bone marrow microenvironment forms a highly specialized niche that houses hematopoietic stem and progenitor cells (HSPCs). Within bone, two anatomically distinct regions, the medullary cavity and the trabecular compartment, differ in their cellular and physical composition, with the potential to differentially regulate influence on resident HSPCs. We hypothesized that HSPCs enriched from the medullary cavity (BM) and trabeculae (TB) represent functionally distinct populations. Contrary to this, functional assessment of HSPCs revealed comparable cellular outputs between BM- and TB-derived HSPCs. To investigate whether microenvironmental signaling contributes to functional regulation, we examined the effects of extracellular vesicles (EVs) isolated from medullary BM and TB. Notably, TB-derived EVs inhibited cell cycle progression, directing HSPCs toward a quiescent state. Together, these findings demonstrate that while isolated BM- and TB-derived HSPCs exhibit similar cell-intrinsic properties, EVs enriched from the TB specifically promote HSPC quiescence, supporting a protective regulatory role for the trabecular microenvironment.