Stem Cell Rev Rep. 2025 Jul 10. doi: 10.1007/s12015-025-10934-4. Online ahead of print.ABSTRACTMesenchymal stem cells (MSCs) have emerged as pivotal tools in biomedical engineering, owing to their remarkable capacity for tissue repair and regeneration. Photobiomodulation (PBM), a non-invasive and safe physical stimulation technique, has demonstrated significant potential in enhancing MSCs' cellular activity, osteogenic differentiation, and therapeutic efficacy. Despite these promising findings, several challenges hinder the clinical translation of PBM, including the optimization of irradiation parameters to maximize therapeutic outcomes and the standardization of protocols to ensure reproducibility and reliability. This review explores the current advancements in PBM technology and its application in MSC research, with a focus on understanding its mechanisms and therapeutic potential. By delving into the fine-tuning of PBM parameters, including cell factor secretion dynamics, signal transduction pathways, and cell-cell interaction networks, we aim to illuminate how PBM modulates the paracrine functions of MSCs. Additionally, the integration of PBM with biomaterials and engineering technologies presents exciting opportunities for bone tissue engineering and cell therapy. Future research should focus on uncovering the mechanisms by which PBM influences MSC behavior, optimizing its therapeutic parameters, and evaluating its safety and long-term benefits. Such efforts will pave the way for PBM's seamless integration into clinical applications, including complex bone defect repair, thereby advancing its role in precision medicine.PMID:40637970 | DOI:10.1007/s12015-025-10934-4