Distinct bone marrow blood vessels differentially regulate haematopoiesis.
Itkin T., Gur-Cohen S., Spencer JA., Schajnovitz A., Ramasamy SK., Kusumbe AP., Ledergor G., Jung Y., Milo I., Poulos MG., Kalinkovich A., Ludin A., Kollet O., Shakhar G., Butler JM., Rafii S., Adams RH., Scadden DT., Lin CP., Lapidot T.
Bone marrow endothelial cells (BMECs) form a network of blood vessels that regulate both leukocyte trafficking and haematopoietic stem and progenitor cell (HSPC) maintenance. However, it is not clear how BMECs balance these dual roles, and whether these events occur at the same vascular site. We found that mammalian bone marrow stem cell maintenance and leukocyte trafficking are regulated by distinct blood vessel types with different permeability properties. Less permeable arterial blood vessels maintain haematopoietic stem cells in a low reactive oxygen species (ROS) state, whereas the more permeable sinusoids promote HSPC activation and are the exclusive site for immature and mature leukocyte trafficking to and from the bone marrow. A functional consequence of high permeability of blood vessels is that exposure to blood plasma increases bone marrow HSPC ROS levels, augmenting their migration and differentiation, while compromising their long-term repopulation and survival. These findings may have relevance for clinical haematopoietic stem cell transplantation and mobilization protocols.