Mesenchymal stromal/stem cell-derived extracellular vesicles as a cell-free therapeutic strategy for traumatic brain injury
Year: 2026
Type: article
Abstract: Traumatic brain injury (TBI) is a leading cause of death and long-term neurological disability worldwide. Beyond the initial sudden mechanical insult, TBI is increasingly recognized as a chronic, multisystem disorder involving complex interactions among neurovascular, immune, and metabolic responses. This perspective helps explain the limited success of single-target neuroprotective therapies and underscores the need for multimodal regenerative strategies. Mesenchymal stromal/stem cells (MSCs) have emerged as promising therapeutic candidates for TBI due to their immunomodulatory and reparative properties, which are largely mediated by their secretome, particularly MSC-derived extracellular vesicles (MSC-EVs). These nanoscale vesicles carry selectively packaged nucleic acids, proteins, metabolites, and lipids from their parent cells, which mediate intercellular communication and induce repair pathways in recipient cells. Accumulating evidence indicates that MSC-EVs can reduce apoptosis and inflammation, promote angiogenesis, neurogenesis, and synaptic plasticity, and improve functional recovery following TBI. This review examines the current understanding of the multiscale pathophysiology of TBI and the role of brain-derived EVs in mediating crosstalk between the injured brain and peripheral systems in post-TBI multiorgan dysfunction, the translational potential of MSC-EVs in TBI, with a focus on EV cargo engineering, targeted delivery mechanisms, emerging therapeutic strategies, combinatorial regenerative strategies, as well as the growing role of artificial intelligence (AI)-assisted bioengineering in optimizing EV-based therapeutics, and considers future research directions that may facilitate clinical translation.
Source: Brain medicine :
DOI: 10.61373/bm026i.0048
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
OpenAlex ID: W7166706428