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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.

Original publication

DOI

10.1038/nature17624

Type

Journal

Nature

Publication Date

21/04/2016

Volume

532

Pages

323 - 328

Keywords

Animals, Antigens, Ly, Arteries, Blood Vessels, Bone Marrow, Bone Marrow Cells, Cell Differentiation, Cell Movement, Cell Self Renewal, Cell Survival, Chemokine CXCL12, Endothelial Cells, Female, Hematopoiesis, Hematopoietic Stem Cell Mobilization, Hematopoietic Stem Cell Transplantation, Hematopoietic Stem Cells, Leukocytes, Male, Membrane Proteins, Mice, Mice, Inbred C57BL, Nestin, Pericytes, Permeability, Plasma, Reactive Oxygen Species, Receptors, CXCR4