Tumor-derived exosomes have emerged as promising liquid biopsy analytes, yet the functional organization of their protein cargo and the identification of biologically meaningful candidates remain inco

The gap

Consensus across the literature

Supporting evidence — 5 representative gaps

• Clinical applications of stem cell-derived exosomes (2024) · doi

  Stem cell therapy multilineage differentiation potential short-lived viability and low engraftment after injection applicable to the treatment for a wide range of diseases stringent storage and transport requirements extensive accumulation of laboratory and clinical data tumorigenic potential easy to isolate and possible for mass-production well-developed regulatory guidelines infusion toxicity immunogenicity ethical issues Stem cell-derived exosome therapy comparable therapeutic effects to stem cells but much smaller batch-to-batch inconsistency more concentrated functional cargos, e.g., cytokines modifiable at its surface and in its cargos versatile delivery modalities stable for long-term storage and transport negligible risk of tumorigenesis and immune response lack of ethical issues no standardized protocol for purification and storage relatively low yield for large scale manufacturing no industry-standard quality specifications insufficient regulatory control exosomes inherit similar therapeutic effects from their parental cell of origin, e.g., tissue regeneration, anti-inflammation and immunomodulation.12,16–18 In this work, we will dissect relevant publications from the last five years in order to present a comprehensive, up-to-date, specialty-specific and disease-oriented review (Fig. 2). Our aim is to bridge the gap that currently exists between surgeons, nanomedicine practitioners, and stem cell researchers. GENERAL BACKGROUND OF EXOSOMES AND EXOSOME THERAPY Biogenesis, composition, and uptake of exosomes Exosomes differ from other types of primary extracellular vesicles (e.g., apoptotic bodies and microvesicles) in terms of size, content, and production mechanism.19 The most popularly accepted mechanism of exosome formation, i.e., an endosomal route, is as follows (Fig. 1a). The initial endosomes are produced by cell membrane invagination during which the bioactive substances begin to accumulate within the early sorting endosomes. The late sorting endosomes then form multivesicular bodies (MVBs) after a second indentation. Finally, fuse with the cell membrane, releasing the carried exosomes to the outside. Non- endosomal such as plasma route of exosome biogenesis, membrane budding, has also been reported.20 the MVBs including proteins, glycoconjugates, As the three major exosome databases (i.e., ExoCarta, Vesicle- pedia, and EVpedia) summarize, exosomes contain numerous molecules, lipids, nucleic acids, metabolites, and other bioactive substances (Fig. 1b). The examples of each category and the corresponding functions have been thoroughly reviewed elsewhere.21,22 On the one hand, exosomes comprise a complex protein network including external proteins (e.g., tetraspanins, antigen-presenting complexes, and adhesion molecules) and internal proteins (e.g., heat shock proteins, ESCRT machinery, cytokines and chemokines, and membrane transporters).23 On the other hand, as the most abundant in human exosomal nucleic acids, microRNA (mRNA) could participate in hematopoiesis, exocytosis, and nerve and vascular cellular communication.24 exosome-mediated regeneration through There are various uptake mechanisms once exosomes reach the recipient cell, all of which can be categorized into membrane fusion, receptor interaction, and internalization21 (Fig. 1b). Finally, the exosomal cargos are released into the cytoplasm, the process of which depends on the source of the exosome, nature of the

  Keywords: exosomes cell exosome membrane stem proteins therapy storage cargos endosomes potential transport production regulatory ethical
• Clinical applications of stem cell-derived exosomes (2024) · doi

  Exosomes have been pursued recently as a cell-free alternative to stem cell-based therapy. ESC-, iPSC-, HSC-, MSC-, NSC- and EPC- derived exosomes are of particular interest, partially due to the pluripotency or multipotency of their parental cells. After going through production and purification with or without modification, stem cell-derived exosomes have demonstrated tremendous potential in treating numerous diseases encountered during surgical practice. These are exemplified by disorders in orthopedic fracture, osteoarthritis, and spinal cord injury); surgery (e.g., neurosurgery (e.g., ischemic stroke, traumatic brain injury, and Alzheimer’s disease); plastic surgery (e.g., wound healing); general surgery (e.g., acute liver injury); cardiothoracic surgery (e.g., myocardial infarction); urology (e.g., chronic kidney disease); head and neck surgery (e.g., sensorineural hearing loss); ophthalmology (e.g., acquired optic neuropathies), and gynecology (e.g., primary ovarian insufficiency). Mechanistically, the diverse therapeutic

  Keywords: surgery exosomes cell injury stem derived cation disease pursued recently free alternative based therapy ipsc
• MSC-derived exosomes ameliorate systemic lupus erythematosus by reprogramming macrophage mitochondrial homeostasis via the CMPK2-cGAS-STING axis (2026) · doi

  Mesenchymal stem cell-derived exosomes (MSC-exo), natural functional nanovesicles, are considered a potent alternative for MSC therapy for the treatment of systemic lupus erythematosus (SLE); however, the molecular mechanisms underlying their therapeutic effects remain elusive.

  Keywords: mesenchymal stem cell derived exosomes natural functional nanovesicles considered potent alternative therapy treatment systemic lupus
• Regenerative Potential of Exosomes from 3D Spheroid-Cultured Stem Cells Compared with 2D Culture in Dentin–Pulp Regeneration: A Systematic Review (2026) · doi

  Future research should focus on standardizing exosome production and characterization protocols, improving methodological rigor, and advancing translational studies, including clinical trials, to validate the therapeutic potential of 3D culture–derived exosomes in dental practice.

  Keywords: future focus standardizing exosome production characterization protocols improving methodological rigor advancing translational including clinical trials
• Systems-Informed prioritization of Exosomal Protein Candidates in TNBC Identifies an ECM Invasion Module and Nominates Agrin as a High-Priority Target (2026) · doi

  Tumor-derived exosomes have emerged as promising liquid biopsy analytes, yet the functional organization of their protein cargo and the identification of biologically meaningful candidates remain incompletely characterized.

  Keywords: tumor derived exosomes emerged promising liquid biopsy analytes functional organization protein cargo identification biologically meaningful