New Cell · Jun 24, 2026
Advances in the study of exercise effects on bone marrow stem cells
By Mithu MM, Efty FT, Munir GAU et al.
Bone marrow stem cells (BMSCs), comprising hematopoietic stem cells (HSCs) and mesenchymal stem cells (MSCs), are essential for hematopoiesis, skeletal remodeling, and systemic metabolic homeostasis. Regular physical activity confers broad health benefits, but its specific effects on BMSC biology have only recently been systematically explored. This review synthesizes current evidence on how exercise modulates BMSC function, emphasizing underlying mechanisms rather than enumerating individual study findings. A literature search of the PubMed database was performed, and 93 relevant studies were analyzed thematically across four mechanistic domains: mechanotransduction, systemic paracrine regulation, metabolic remodeling, and niche microenvironmental changes. The evidence indicates that exercise exerts multi-level effects on BMSCs through integrated biomechanical, paracrine, and metabolic pathways. Key mechanisms include Piezo1-mediated mechanosensing, Wnt/β-catenin and STAT3 signaling, irisin-mediated autophagy activation, and metabolic coupling via reticulocalbin-2. These pathways converge to enhance proliferative capacity, shift differentiation commitment toward osteogenesis and away from adipogenesis, and remodel the bone marrow niche. However, the evidence base is constrained by considerable methodological heterogeneity including variations in exercise type, intensity, duration, and subject age/sex as well as limited human translational data. Contradictory findings (e.g., adverse effects under caloric restriction) highlight the context-dependence of exercise benefits. Future research should prioritize standardized protocols, mechanistic elucidation of intensity- and duration-specific effects, and well-controlled human trials to establish evidence-based exercise prescriptions for conditions involving BMSC dysfunction, including osteoporosis, diabetes, and bone marrow failure syndromes.