Mesenchymal stromal cells therapy for remodeling the joint microenvironment: mechanisms, nanotechnology-enhanced strategies, and translation prospects.

Osteoarthritis (OA) is a complex, multifactorial whole-joint disease characterized by progressive articular cartilage degeneration, synovitis, and subchondral bone remodeling. Current clinical interventions primarily offer symptomatic management but do not halt or reverse disease progression. Recent advancements in regenerative medicine have emphasized mesenchymal stromal cell (MSC) therapy owing to its substantial potential in tissue repair and microenvironmental modulation. This review systematically evaluates the therapeutic efficacy and potential mechanisms of bone marrow-derived MSCs, adipose-derived stromal cells, umbilical cord-derived MSCs, synovium-derived MSCs, embryonic stem cell-derived MSCs and induced pluripotent stem cell-derived MSCs, as well as MSC-derived exosomes, in modulating the joint microenvironment. Furthermore, we discuss recent innovations in nanotechnology-enhanced strategies, designed to improve targeting specificity and therapeutic durability of MSC-based interventions. This review aims to establish a foundational framework and translational roadmap for the development of next-generation disease-modifying therapies for OA.