Hartman Institute for Therapeutic Organ Regeneration

Distinct bone marrow blood vessels differentially regulate haematopoiesis.

TitleDistinct bone marrow blood vessels differentially regulate haematopoiesis.
Publication TypeJournal Article
Year of Publication2016
AuthorsItkin 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
JournalNature
Volume532
Issue7599
Pagination323-8
Date Published2016 Apr 21
ISSN1476-4687
KeywordsAnimals, 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
Abstract

<p>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.</p>

DOI10.1038/nature17624
Alternate JournalNature
PubMed ID27074509
PubMed Central IDPMC6450701
Grant ListR01 EB017274 / EB / NIBIB NIH HHS / United States
U01 HL100402 / HL / NHLBI NIH HHS / United States
EB017274 / EB / NIBIB NIH HHS / United States
HL100402 / HL / NHLBI NIH HHS / United States

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