In vivo polarization of M2 macrophages by mesenchymal stem cell-derived extracellular vesicles: A novel approach to macrophage polarization and its potential in treating inflammatory diseases

•Uncontrolled inflammatory immune responses lead to a wide range of inflammatory diseases.•Macrophages based on their phenotype (M1 and M2) have a critical role in exacerbating or mitigating inflammatory disease, respectively.•Mesenchymal stem cells (MSC)-derived extracellular vesicles (EVs) offer a promising approach to inducing M2 polarization in macrophages.•Invivo-induced M2 macrophages by MSC-derived EVs ameliorate inflammation-associated diseases. Inflammation is a physiological process of the immune system, which, if it persists chronically, can contribute to inflammation-related diseases. Macrophages have a critical role in inflammation, as they undergo differentiation into M1 phenotype. One approach to managing inflammation related diseases involves the utilization of M2 macrophages and their transplantation into the host. However, the in vivo application of mediators that can induce M2 polarization faces limitations. In recent years, it has been acknowledged that extracellular vesicles originating from mesenchymal stem cells possess favorable biocompatibility, enabling their facile in vivo utilities. This study hypothesizes that MSC-derived EVs can induce M2 macrophages in vivo, then these macrophages will be used for mitigating inflammatory conditions in many clinical conditions. These vesicles exhibit the capability to enhance M2 polarization of macrophages, therefore, representing a potential therapeutic tool for modulating macrophage function in vivo, ensuring a safer application of manipulated macrophages in diseases associated with inflammation.