Demystifying Our Knowledge of Stem Cells and Progenitor Cells Part I: Basic Concepts Relevant to the Treatment of Osteonecrosis and Other Diseases of the Musculoskeletal System.

BACKGROUND: The fundamental biological principles underlying bone healing are highly relevant to the treatment of osteonecrosis, the local death of bone marrow commonly due to the use of corticosteroids or excessive alcohol.

METHODS: Injury to bone initiates a preprogrammed series of events that are sensed by resident macrophages or osteomacs, and subsequently involve cells of the hematopoietic, mesenchymal, and angiogenic lineages. Intercellular crosstalk among macrophages and other immune cells, osteoclasts, mesenchymal stem cells, and angiogenic precursors creates a local microenvironment for the resolution of inflammation, resorption of the necrotic bone, osteogenesis, and angiogenesis.

RESULTS: Strategies to mitigate inflammation and promote bone healing include systemic or local delivery of biomolecules, local application of cell-based and cell-free (i.e., cell by-products such as exosomes) therapies, and gene therapy. In the United States, cell therapies cannot include culturing or altering the cells via "manipulation" of their physical, chemical, or functional state. Thus, bone marrow aspirate concentrate is often used as a bone graft substitute.

CONCLUSIONS: Further preclinical research and rigorous clinical trials are necessary to demonstrate safe, efficacious, and cost-effective therapies to enhance bone healing and improve clinical outcomes in early-stage osteonecrosis, where the joint is still salvageable.