Stem cells reside in a specialized, regulatory environment termed “niche” that dictates how they generate, maintain, and repair tissues. We have previously documented in living animals that transplanted stem/progenitor populations (HSPC) localize to sub-domains of marrow microvessels, where CXCL12 is particularly abundant. We have now used high-resolution combined confocal and two-photon video imaging of individual hematopoietic cells in the calvarium bone marrow of living animals over time to examine the relationship of stem and progenitor cells to blood vessels, osteoblasts, and endosteal surfaces as they home and engraft. Osteoblasts were enmeshed in microvessels, and relative positioning of stem/progenitor cells within this complex tissue was non-random and dynamic. Both cell autonomous and non-autonomous factors influenced primitive cell localization. Different hematopoietic cell subsets localized to distinct locations according to the stage of differentiation. In settings of engraftment as well as expansion, marrow stem/progenitor cells were in closer proximity to bone and osteoblasts. The hematopoietic stem/progenitor cell niche is both perivascular and periendosteal in trabecular bone with physiologic demand influencing closer positioning of stem cells to bone.
Disclosures: Scadden:Genzyme, Inc.: Consultancy; Fate Therapeutics, Inc.: Employment, Equity Ownership, consultant. Off Label Use: PTH effect on osteoblasts PGEZ effect on stem cells.
