BEYOND CELLS: THE EMERGING ROLE OF MESENCHYMAL STROMAL CELL–DERIVED EXTRACELLULAR VESICLES IN THE RESPIRATORY SYSTEM

For decades, cell-based therapies have been viewed as a promising strategy to repair injured lung tissue. Yet, much of their benefit appears not to depend on  cell engraftment, but on what cells release. This realization has shifted attention  toward extracellular vesicles (EVs) derived from mesenchymal stromal cells  (MSCs) as key biological effectors.  MSC-derived EVs act as highly specialized carriers of biological information.  They transport proteins, lipids, and regulatory RNAs capable of reprogramming  target cells and modulating complex pathways in inflammation, immunity, and  tissue repair. In the respiratory system, these vesicles orchestrate  communication between epithelial, endothelial, and immune cells, shaping the  response to injury at multiple levels. In experimental models of acute respiratory distress syndrome, asthma, and  emphysema, MSC-derived EVs consistently attenuate inflammation, restore  alveolar–capillary barrier function, enhance bacterial clearance, and limit fibrotic  remodeling. These effects are achieved through coordinated mechanisms,  including macrophage reprogramming, mitochondrial transfer, and delivery of  anti-inflammatory microRNAs. Importantly, EVs reproduce many of the  therapeutic benefits of their parent cells while avoiding key limitations of cell based therapies, such as immunogenicity, tumorigenicity, and challenges  related to storage and delivery. Beyond therapy, EVs are emerging as powerful biomarkers. Their cargo reflects  the physiological state of the cells of origin, offering a dynamic and minimally  invasive window into lung injury and repair. This dual role, as both mediators  and messengers, positions EVs at the interface between diagnosis and  treatment. However, translation to clinical practice remains challenging. Standardization of  isolation techniques, characterization of vesicle subpopulations, dosing  strategies, and large-scale manufacturing are critical hurdles that must be  addressed before widespread clinical application. This field is rapidly redefining how we think about regenerative therapy in the  lung. Moving from cells to cell-derived signals opens a new therapeutic  paradigm, one that is potentially safer, more controllable, and more precise.  MSC-derived extracellular vesicles are not simply an alternative to cell therapy;  they represent a fundamental shift in how we approach lung repair and  modulation of disease.