Work

Extracellular Vesicles for Therapeutic Applications: A Translational Framework Integrating Sources, Administration Routes, Indications, Quality Control, and Regulatory Systems

Year: 2026

Type: review

Abstract: : Extracellular vesicles (EVs) are nanoscale membranous vesicles that mediate intercellular communication via the transport of bioactive cargos. With context-dependent intrinsic targeting, source- and cargo-dependent favorable biocompatibility and loading capacity, EVs represent promising acellular therapeutic platforms with context-dependent translational potential. However, their clinical application is hindered by source-associated functional heterogeneity, unclear matching relationships between administration routes and disease indications, as well as imperfect quality control specifications and fragmented global regulatory frameworks alongside insufficient clinical trial data. This review systematically summarizes the biological features of EVs originating from mesenchymal stem cells, immune cells, tumor cells, plants, milk, microbes and platelets, and compares the pros and cons and applicable scenarios of intravenous, oral, nasal, inhaled, and multiple local injection delivery modalities. We further recapitulate the research progress of EV therapeutics across regenerative medicine, immunotherapy, oncology, neurological and metabolic disorders, and analyze worldwide regulatory policies while sorting out the up-to-date industrial-sponsored global clinical pipeline updated to April 2026. Centered on a core five-dimensional matching framework integrating EV sources, administration routes, disease indications, critical quality attributes (CQAs) and global regulatory requirements, this work elaborates current translational bottlenecks and commercialization obstacles of EV products. This review provides theoretical support for precision EV therapy optimization, unified quality criterion establishment, international regulatory coordination and accelerated clinical and industrial transformation of EV-based medicines. The diagram outlines a framework for using extracellular vesicles (EVs) in therapy, detailing sources, administration methods and therapeutic uses. EVs originate from mesenchymal stem cells, immune cells, tumor cells, edible plants, microbes, bovine milk and others like platelets and neural stem cells. Engineering modifications include gene and targeting ligand modifications and drug loading. Administration is categorized into systemic (intravenous, oral), non-invasive local (nasal, aerosol) and invasive local (subcutaneous, intravitreal, intrathecal, intra-articular, intraperitoneal) methods. Therapeutic uses cover tissue repair, immune regulation, tumor therapy, neurological and metabolic diseases and others such as intervertebral disc degeneration, bone regeneration, anti-infection, respiratory and eye diseases.A translational framework for extracellular vesicles: sources, administration routes and therapeutic applications. Keywords: extracellular vesicles, source heterogeneity, administration route, precision therapy, clinical translation, regulatory specification

Source: International Journal of Nanomedicine

DOI: 10.2147/ijn.s622474