Priming effect of photobiomodulation of mesenchymal stem cells on extracellular vesicles for regenerative medicine.

Extracellular vesicles (EVs) derived from mesenchymal stem cells (MSCs) (MSCs-derived EVs) have shown promising outcomes in repairing damaged tissues across various disease models. Combining MSCs-derived EVs with advanced technologies could further enhance their use as a viable cell-free therapy in medical applications. Photobiomodulation (PBM) has shown a synergistic effect with EVs in improving tissue regeneration. This pioneer review aimed to evaluate the entire scope available in the current literature on the PBM priming effect on MSCs-derived EVs. Two independent reviewers conducted a literature search in online databases PubMed/MEDLINE, Web of Science, Scopus, EMBASE and LIVIVO. The inclusion criteria were: (1) studies investigating PBM and MSCs-derived EVs and (2) all language and data. Of 213 found articles, 8 (eight) articles were selected for a complete reading. After the complete reading, 6 (six) articles were selected for data extraction. In general, the studies reported no deleterious effects of PBM on EVs. Furthermore, in vitro, PBM increased concentration of EVs, angiogenic factors, anti-apoptotic protein levels and cell survival. In vivo, PBM and EVs demonstrated positive effects in skin wound healing and pulp regeneration. These studies highlighted the promising potential of combining both therapies (PBM and MSCs-derived EVs) as an innovative strategy in regenerative medicine. However, significant challenges remain, including the need for standardization of EVs isolation and characterization methods, as well as the evaluation of laser irradiation parameters across diverse experimental conditions. Additionally, a deeper understanding of the underlying mechanisms of PBM effects on EVs is crucial to optimize this approach and fully harness its therapeutic potential.