Mesenchymal stem cells (MSCs) are central effectors in regenerative medicine, yet their clinical translation is hindered by inconsistent therapeutic outcomes and a lack of standardized light-delivery protocols. This review addresses an underexplored dimension of photobiomodulation (PBM): the divergent, wavelength-dependent signaling programs triggered in MSCs by red/near-infrared (NIR) versus blue light. By integrating biophysical principles of light delivery with a systems biology analysis of protein–protein interaction networks (STRING/GO), we delineate a “Dual Photonic Programming” framework. Red/NIR light (600–1100 nm) targets mitochondrial cytochrome c oxidase, activating a bioenergetic-anabolic program centered on PI3K/Akt/mTOR and Wnt/β-catenin—pathways essential for structural tissue repair. Blue light (400–500 nm) engages cytosolic flavins to drive a secretory-paracrine program that modulates vesicle trafficking and immunomodulatory cargo release. We further examine the dosimetric paradox, demonstrating how culture-environment optics and the Arndt–Schultz biphasic law govern the transition from regenerative stimulation to inhibitory oxidative stress. By tailoring photonic parameters to the MSC’s anatomical origin and metabolic baseline, PBM can serve as a high-fidelity bio-switch for orchestrated tissue repair, providing a mechanistic roadmap for standardized regenerative therapies.
Amouroux et al. (Fri,) studied this question.