Photobiomodulation of mineralisation in mesenchymal stem cells

Abstract

Mesenchymal stem cells (MSCs) and photobiomodulation (PBM) both offer significant therapeutic potential in regenerative medicine. MSCs have the ability to self-renew and differentiate; giving rise to multiple cellular and tissue lineages that are utilised in repair and regeneration of damaged tissues. PBM utilises light energy delivered at a range of wavelengths to promote wound healing. The positive effects of light on MSC proliferation are well documented; and recently, several studies have determined the outcomes of PBM on mineralised tissue differentiation in MSC populations. As PBM effects are biphasic, it is important to understand the underlying cellular regulatory mechanisms, as well as, provide accurate details of the irradiation conditions, to optimise and standardise outcomes. This review article focuses on the use of red, near-infra-red (R/NIR) and blue wavelengths to promote the mineralisation potential of MSCs; and also reports on the possible molecular mechanisms which underpin transduction of these effects. A variety of potential photon absorbers have been identified which are reported to mediate the signalling mechanisms, including respiratory chain enzymes, flavins, and cryptochromes. Studies report that R/NIR and blue light stimulate MSC differentiation by enhancing respiratory chain activity and increasing reactive oxygen species levels; however, currently, there are considerable variations between irradiation parameters reported. We conclude that due to its non-invasive properties, PBM may, following optimisation, provide an efficient therapeutic approach to clinically support MSC-mediated hard tissue repair. However, to optimise application, further studies are required to identify appropriate light delivery parameters, as well as elucidate the photo-signalling mechanisms involved.

The Effects of 5% 5-Aminolevulinic Acid Gel and Red Light (ALAD-PDT) on Human Fibroblasts and Osteoblasts

“…ALAD alone (100-ALAD) also increased the production of ROS at 10 and 20 min ( Figure 6 A), whereas in HOB, ALAD-PDT significantly stimulated the ROS after 30 min in respect to basal concentrations of ROS in control cells ( Figure 6 B). The ROS levels in both cells showed a similar result to the control group by 1 h after the photodynamic protocol, and also remained at the basal level at 24 h. Studies have shown that high levels of ROS can cause cell death, but ROS are also important mediators of intracellular signaling [ 29 , 30 , 31 ]. Although the detailed mechanism has yet to be revealed, Kushibiki et al showed that PDT promotes murine osteoblasts differentiation via AP-1 that is upregulated by high ROS production [ 24 ].…”

Low intensity near-infrared light promotes bone regeneration via circadian clock protein cryptochrome 1

“…The combined use of mesenchymal stem cells (MSCs) and photobiomodulation (PBM) offers strategies with great therapeutic potential for regenerative medicine. 50 In this study, we successfully demonstrated the effect of 810 nm low-intensity NIR light on bone regeneration, and elucidated the mechanism by which light activates the BMP signaling pathways by promoting the ubiquitin-dependent degradation of CRY1, providing a novel clinical application of non-invasive NIR treatment in bone defects (Fig. 6 ).…”

Functional Hydrogels and Their Applications in Craniomaxillofacial Bone Regeneration

“…(ii) When considering the addition of nanoparticles, the unique properties of nanoparticles should be considered, such as gMPs and pMPs with different degradation rates for sequential drug release in hydrogel delivery systems [ 70 ] and the loading of metal oxides for the continuous delivery of Mg 2+ [ 69 , 73 ]. In addition, studies on functionalized nanoparticles should be discussed; for example, NIR has better tissue penetration [ 59 ], and even the potential of NIR to induce osteogenic differentiation of MSCs has been reported [ 88 ], and its ability to penetrate the patient’s scalp to irradiate cranial defects in clinical practice deserves to be evaluated. NIR likewise provides inspiration as to whether upconverting nanoparticles can be introduced for the preparation of NIR-responsive hydrogel systems.…”