Dynamic crosstalk between Tspan4+ macrophage subsets and MSCs via migrasomes orchestrates fracture repair

Through single - cell sequencing, it was ascertained that macrophages highly expressed Tspan4 during the fracture healing process and could be categorized into Tspan4⁺Lyve1⁺ macrophages and Tspan4⁺Mpeg1⁺ macrophages. By means of cell - communication analysis, Tspan4⁺Lyve1⁺ macrophages and Tspan4⁺Mpeg1⁺ macrophages were proposed to interact with MSCs via Gas6 - Axl and IL1b - IL1r1, respectively. Collectively, macrophage-derived migrasomes convey IL-1β to MSCs to activate AMPK, thereby enhancing BMSC migration and likely osteogenic priming during fracture repair. These findings identify migrasomes as a previously underappreciated conduit in macrophage-BMSC crosstalk and suggest a vesicle-based strategy to improve fracture healing.