Aortic Tissue as a Niche for Hematopoiesis

The stem cell theory of hematopoiesis predicts that all mature blood cell lineages circulating in the bloodstream or resident in tissues arise via a hierarchy of hematopoietic progenitor cell (HPC) intermediates that are ultimately derived from hematopoietic stem cells (HSC). In the adult human, bone marrow–resident HSC and HPC generate billions of circulating blood cells daily, ranging from the short-lived neutrophils and platelets to long-lived B and T lymphocytes and monocyte macrophages. Recent interest in the roles of macrophages as modulators of angiogenesis1 and as participants in atheroma formation2 highlight the need to better understand the mechanisms of recruitment and retention of macrophages and their progenitor precursors within tissues. In this issue of Circulation , Psaltis and colleagues3 identify clonogenic HPC activity in aortic adventitia (that is enriched in HPC compared with peripheral blood or muscle tissue), which appears skewed toward colony-forming unit-macrophage (CFU-M) differentiation. In addition, stem cell antigen-1–expressing cells in the aortic adventitia coexpressed a variety of HSC antigens, and adoptive transfer of these cells into irradiated recipient mice led to low but sustained multilineage reconstitution, a property of HSC. Although bone marrow (BM)–derived donor hematopoietic cells reconstituted the aorta of lethally irradiated animals, the majority of aorta-derived CFU-M appeared to be constitutive or long term residents of the vessel wall (with sustained but only partial replacement from donor BM cells), suggesting that either the aortic adventitial microenvironment imparts specific differentiation properties to marrow-derived precursors or that a local origin for HSC/HPC exists in the adult vasculature. Is there any evidence to suggest that HSC/HPC may originate and/or migrate through the aortic adventitia?Article see p 592Hematopoiesis occurs in a site- and tissue-specific pattern that varies throughout mammalian development. The first blood cells (including macrophages) arise in the extraembryonic yolk sac, and the yolk …