Bone marrow mesenchymal stem cell exosomes in osteonecrosis: pathological mechanisms and therapeutic strategies

Osteonecrosis is bone death caused by disrupted blood supply. It often leads to bone collapse and joint failure. Current treatments ease symptoms but cannot reverse dead bone tissue. They also have high recurrence rates. Bone marrow-derived mesenchymal stem cell exosomes (BMSC-Exos) are natural carriers. They mediate cell communication. Preclinical studies suggest they modulate osteoclast and osteoblast activity. They may also influence cell death pathways. But direct evidence in human osteonecrosis remains limited. BMSC-Exos have safety and immune compatibility advantages over conventional cell therapies in animal models. Yet clinical application faces major barriers. Existing reviews have not fully addressed them. Recent reviews treat mesenchymal stem cell exosomes(MSC-Exos) from different sources as the same. They discuss osteonecrosis as a uniform target. They overlook lesion zones, source-specific bone-forming bias, and production barriers. This review examines the gap between preclinical findings and clinical use. It focuses on three areas: (1) spatial variation of necrotic lesions and delivery needs; (2) the bone marrow niche advantage of BMSC-Exos versus adipose-derived stem cells(ADSC-) or umbilical cord-derived(UC-) MSC-Exos; and (3) unresolved barriers in standardized production, potency testing, and stage-specific strategy validation.