In recent years, the discovery of migrasomes—a novel class of extracellular vesicles formed during cell migration—has revolutionized our understanding of intercellular communication and cellular homeostasis. These burgeoning vesicular structures, first identified only a few years ago, have rapidly become the focus of intense scientific scrutiny due to their multifaceted roles in diverse biological phenomena, ranging from embryonic development to disease pathogenesis. Migrasomes are not mere cellular debris or passive carriers; instead, they function as sophisticated, spatially precise signaling hubs capable of transferring complex molecular cargo, thereby orchestrating cellular behavior and tissue morphogenesis in ways previously unimagined.

At the core of migrasome biology lies their intimate association with cell migration. Unlike traditional extracellular vesicles, migrasomes bud off from retraction fibers—the elongated trailing structures left behind migrating cells—rendering migrasomes inherently connected to the dynamic migratory processes of cells. This unique biogenesis imparts migrasomes with distinct molecular compositions and functional capabilities, positioning them as pivotal mediators of cell-to-cell communication. They encapsulate a rich repertoire of bioactive molecules including cytokines, chemokines, growth factors, proteins, and even full-length mRNAs that influence a myriad of recipient cell functions upon delivery.

The importance of migrasomes in cellular communication is exemplified by their role in guiding embryonic precursor cells during development. One compelling model involves the chemokine CXCL12, highly enriched within migrasomes produced by migrating cells in zebrafish embryos. These CXCL12-laden migrasomes accumulate beneath embryonic structures such as the shield during gastrulation, creating localized signaling centers that interact with CXCR4 receptors on dorsal forerunner cells (DFCs). This interaction cues the directed migration and proper localization of precursor cells, underpinning the formation of organs with correct spatial orientation. Disruption of this migrasome-chemokine axis results in profound developmental abnormalities, underscoring migrasomes’ indispensable role in morphogenesis.

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Beyond embryogenesis, migrasomes offer an unparalleled means for lateral transfer of molecular information between cells. Dendritic cells, key players of the immune system, exploit migrasomes to shuttle antigenic peptides and chemokines among one another, modulating immune surveillance and activation. Further illustrating their versatility, migrasomes secreted by neutrophils in response to traumatic brain injury convey crucial signals to microglia, the central nervous system’s resident immune cells, potentially modulating neuroinflammatory responses and tissue repair. The molecular cargo within migrasomes extends beyond proteins; they carry mRNAs that can be translated upon uptake by recipient cells, as demonstrated by the transfer of Pten mRNA restoring tumor suppressor functions in PTEN-deficient cancer cells, thereby selectively attenuating oncogenic signaling pathways.

The biogenesis of migrasomes is intricately linked to the mechanical and metabolic demands of migrating cells, which often suffer elevated mitochondrial stress. This stress triggers a fascinating quality-control mechanism known as mitocytosis, in which damaged mitochondria are selectively trafficked to the cell periphery and sequestered into migrasomes for extrusion. This process—mediated by differential motor protein engagement—ensures cellular mitochondrial health is maintained by expelling dysfunctional organelles, thereby preserving metabolic homeostasis. Intriguingly, migrasomes also encapsulate other organelles such as autophagosomes, lysosomes, and lipid droplets, hinting at a broader role in homeostatic maintenance beyond mitochondrial quality control. The mechanistic intricacies of how these vesicles manage a diverse set of intracellular components to alleviate cellular stress remain a fertile area for future research.

Migrasomes’ contributions extend beyond the cellular level to encompass systemic physiological processes. In the cardiovascular sphere, tetraspanins—critical structural molecules constituting migrasomes—play documented roles in angiogenesis, thrombosis, and vascular repair mechanisms. These findings suggest that migrasome dynamics significantly impact vascular homeostasis, influencing both development and response to injury. Similarly, within the nervous system, migrasomes regulate the migratory behavior of neural crest cells, pivotal for craniofacial development, further substantiating their role in maintaining tissue integrity and function.

A particularly enthralling aspect of migrasome biology is their ability to deliver signals with spatial and temporal precision to defined anatomical locales. This targeted delivery system fosters intricate biological patterns such as those seen in zebrafish gastrulation, where migrasomes form clustered reserves of signaling molecules beneath the embryonic shield. These localized gradients of chemokines and growth factors guide cellular migrations essential for organogenesis and the establishment of body asymmetry. The loss of migrasome production or function disrupts these gradients, leading to aberrant tissue patterning and organ misplacement.

In avian models, the spatial roles of migrasomes take on a different dimension. Migrasomes produced by migrating monocytes along the chicken chorioallantoic membrane adhere to the extracellular matrix, laying down linear trails rich in pro-angiogenic factors such as VEGFA and CXCL12. These migrasome tracks furnish the microenvironment necessary for capillary sprouting and vascular network formation, highlighting the versatility of migrasomes as not only agents of chemotaxis but architects of tissue structural organization.

The emerging evidence from mesenchymal stromal cells (MSCs) further illustrates migrasomes’ significance in developmental biology and immune regulation. MSC-derived migrasomes bearing stromal cell-derived factor 1 (SDF-1) act as chemoattractants for hematopoietic progenitors, orchestrating stem cell niches’ assembly during bone marrow development. This function exemplifies migrasomes’ multifaceted role not only in embryogenesis but also in sustaining adult tissue homeostasis and regenerative processes.

From a clinical perspective, the ability of migrasomes to selectively package and transfer functional mRNAs and proteins harbors immense therapeutic potential. The demonstrated restoration of tumor suppressor activity in oncogene-addicted cancer cells via migrasome-mediated Pten mRNA delivery spotlights a novel avenue for precision molecular therapy. Furthermore, elucidating the mechanisms by which migrasomes evade degradative pathways within recipient cells to enable mRNA translation could inspire innovative drug delivery platforms, particularly for diseases rooted in signaling defects or impaired cell migration.

Nonetheless, several pivotal questions linger regarding migrasome biology. Are migrasomes predominantly a cellular garbage disposal system, expelling dysfunctional components like damaged mitochondria, or do they equally serve as “supply stations,” delivering healthy organelles or essential signaling molecules to support recipient cells? The balance between these roles remains to be precisely defined. Moreover, the molecular machinery governing cargo selection and packaging into migrasomes—allowing the enrichment of specific mRNAs and organelles—is only beginning to be understood. Future studies dissecting migrasome biogenesis at the molecular level will be critical for leveraging their potential in biomedical applications.

In sum, migrasomes represent a groundbreaking paradigm in cell biology. Their discovery has unveiled a sophisticated platform that integrates the dynamic movements of migrating cells with precise intercellular signaling and homeostatic regulation. By controlling embryonic development, immune responses, mitochondrial quality, and vascular remodeling, migrasomes have emerged as key orchestrators of complex multicellular processes. Given their emerging roles across multiple physiological systems and their implications in diseases ranging from cancer to neuroinflammation, migrasomes hold promise as both diagnostic biomarkers and therapeutic vehicles.

As research continues to unravel the complexities of migrasome function, the prospect of harnessing these vesicles for targeted drug delivery, tissue engineering, and regenerative medicine becomes increasingly tangible. The intersection of migrasome biology with cutting-edge biomedical technologies heralds a new frontier where cellular migration, molecular communication, and therapeutic intervention converge. The challenge now lies in translating these insights into clinical realities that can transform patient outcomes across a spectrum of diseases.

Ultimately, migrasomes do not merely represent an additional facet of extracellular vesicle biology; they redefine the landscape of cellular interaction and communication. Their capacity to deliver targeted, spatially localized signals while modulating intracellular homeostasis exemplifies nature’s ingenuity in coordinating cellular and tissue function. The next decade of research promises to unveil even deeper layers of migrasome complexity, reshaping our fundamental understanding of biology and medicine.

Subject of Research: The biogenesis and biological roles of migrasomes

Article Title: The biogenesis and biological roles of migrasomes in human diseases

Article References: Zhang, Y., Chen, W., Zhu, J. et al. The biogenesis and biological roles of migrasomes in human diseases. Cell Death Discov. 11, 296 (2025). https://doi.org/10.1038/s41420-025-02569-8

Image Credits: AI Generated

DOI: https://doi.org/10.1038/s41420-025-02569-8

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