Enhancing osteoporosis treatment with engineered mesenchymal stem cell-derived extracellular vesicles: mechanisms and advances

As societal aging intensifies, the incidence of osteoporosis (OP) continually rises. OP is a skeletal disorder characterized by reduced bone mass, deteriorated bone tissue microstructure, and consequently increased bone fragility and fracture susceptibility, typically evaluated using bone mineral density (BMD) and T-score. Not only does OP diminish patients’ quality of life, but it also imposes a substantial economic burden on society. Conventional pharmacological treatments yield limited efficacy and severe adverse reactions. In contemporary academic discourse, mesenchymal stem cells (MSCs) derived extracellular vesicles (EVs) have surfaced as auspicious novel therapeutic modalities for OP. EVs can convey information through the cargo they carry and have been demonstrated to be a crucial medium for intercellular communication, playing a significant role in maintaining the homeostasis of the bone microenvironment. Furthermore, various research findings provide evidence that engineered strategies can enhance the therapeutic effects of EVs in OP treatment. While numerous reviews have explored the progress and potential of EVs in treating degenerative bone diseases, research on using EVs to address OP remains in the early stages of basic experimentation. This paper reviews advancements in utilizing MSCs and their derived EVs for OP treatment. It systematically examines the most extensively researched MSC-derived EVs for treating OP, delving not only into the molecular mechanisms of EV-based OP therapy but also conducting a comparative analysis of the strengths and limitations of EVs sourced from various cell origins. Additionally, the paper emphasizes the technical and engineering strategies necessary for leveraging EVs in OP treatment, offering insights and recommendations for future research endeavors.