Emerging roles of migrasomes in blood-tissue barrier integrity and intercellular signaling

Migrasomes are a newly recognized class of migration-dependent organelles that arise along retraction fibers of migrating cells and are released into the extracellular milieu. Structurally and biogenetically distinct from extracellular vesicles, migrasomes function as signaling hubs that mediate localized transfer of bioactive cargo and coordinate intercellular communication. Accumulating evidence indicates that migrasomes participate in diverse biological processes, including developmental patterning, immune regulation, and tumor progression. Blood-tissue barriers (including the blood-brain, glomerular, thymic, retinal, and placental barriers) are specialized interfaces that regulate molecular and cellular exchange between the circulation and tissues. These barriers rely on tightly coordinated interactions among barrier-forming endothelial cells, junctional complexes, basement membranes, and supporting stromal components to preserve tissue homeostasis. Despite emerging studies on migrasome biology, a comprehensive mechanistic understanding of migrasome-barrier interactions across the full spectrum of blood-tissue barrier systems remains lacking. This review addresses that gap by proposing an integrative conceptual framework for migrasome signaling within barrier microenvironments, examining how migrasome-mediated signaling influences cellular crosstalk and functional regulation within these interfaces in both health and disease. We also discuss technological advances, current limitations, and key knowledge gaps, highlighting the need for barrier-focused mechanistic studies to determine whether migrasomes act as active regulators of barrier integrity and signaling or represent secondary byproducts of cellular migration within barrier microenvironments.