Mesenchymal stem cells in bone regeneration: an organellar perspective.

Mesenchymal stem cells (MSCs) contribute substantially to bone regeneration, yet osteogenic cues alone do not fully explain how their reparative capacity is established, maintained, or lost. Prior studies show that organelles, especially mitochondria, play critical roles in MSC osteogenesis. Recent advances reveal that individual organelle states, inter-organelle coordination within MSCs, and reciprocal organelle-related intercellular communication together constitute an integrated regulatory network. In this review, we introduce 'organellar governance' as a framework for understanding MSC-mediated bone regeneration. We discuss how adaptive organelle remodeling supports osteogenesis and how organelle regulation is disrupted in disease. We further address reciprocal organelle-related intercellular communication and organelle-directed therapeutics for MSC-mediated bone regeneration. These insights provide a network-level perspective and highlight broader translational significance for regenerative medicine.