Skeletal Stem/osteoprogenitor Cells: Current Concepts, Alternate Hypotheses, and Relationship to the Bone Remodeling Compartment

Plastic adherent bone marrow stromal cells have become synonymous with skeletal stem cells, and perhaps rightfully so, as these cells have been extremely well characterized over the past four decades, since their original description by Friedenstein. However, although this cell population is useful as an experimental model of precursors for osteoblasts and other mesenchymal lineages, the precise role of bone marrow stromal cells in bone remodeling, fracture repair, or repair of non-skeletal tissues remains unclear. Moreover, there is a conceptual problem in terms of postulating that these cells are osteoblast precursors at sites of bone remodeling on trabecular surfaces adjacent to red marrow and yet having to posit potentially entirely different mechanisms for the origins of osteoblasts at sites of cortical bone remodeling distant from red marrow. Thus, the identification and characterization in recent years of non-adherent stem and osteoprogenitor cells in the bone marrow, of similar cells in the peripheral circulation, and of stem/osteoprogenitor cells arising either from the perivascular compartment (pericytes) or within the developing vascular wall itself, has suggested alternative candidate cell populations that may help to resolve the problem of postulating different mechanisms of remodeling in trabecular versus cortical bone. When coupled with our evolving understanding of the bone remodeling compartment (BRC), a closed cavity penetrated by capillaries which appears to be the site of remodeling in both trabecular and cortical bone, it is likely that our conceptual understanding of the fundamental mechanisms of bone remodeling will need to be modified.