Photobiomodulation has rejuvenating effects on aged bone marrow mesenchymal stem cells

Abstract

The plasticity and proliferative capacity of stem cells decrease with aging, compromising their tissue regenerative potential and therapeutic applications. This decline is directly linked to mitochondrial dysfunction. Here, we present an effective strategy to reverse aging of mouse bone marrow mesenchymal stem cells (BM-MSCs) by restoring their mitochondrial functionality using photobiomodulation (PBM) therapy. Following the characterization of young and aged MSCs, our results show that a near-infrared PBM treatment delivering 3 J/cm2 is the most effective modality for improving mitochondrial functionality and aging markers. Furthermore, our results unveil that young and aged MSCs respond differently to the same modality of PBM: whereas the beneficial effect of a single PBM treatment dissipates within 7 h in aged stem cells, it is lasting in young ones. Nevertheless, by applying three consecutive treatments at 24-h intervals, we were able to obtain a lasting rejuvenating effect on aged MSCs. Our findings are of particular significance for improving autologous stem cell transplantation in older individuals who need such therapies most.

Steering the multipotent mesenchymal cells towards an anti-inflammatory and osteogenic bias via photobiomodulation therapy: How to kill two birds with one stone

“…In this regard, 808-nm light has been shown to interact with mitochondria complex IV cytochromes and partially with complex III, thereby affecting the energetic metabolism of extracted mitochondria. 62 Eroglu et al 8 have also described that effect on MSCs. In a unicellular model, light delivered at a fluence of 3 and 60 J/cm 2 affected mitochondrial metabolism differently.…”

“…Additionally, as described above, young and aged MSCs irradiated with near-infrared light at 808-nm and a fluence of 3 J/cm 2 for 3 h exhibited improvement in mitochondrial activities. 8 Moreover, two or three consecutive laser treatments considerably enhanced the proliferative capacity of both young and aged MSCs on day 7. These findings suggest that pertinent laser therapy re-establishes mitochondrial respiration and facilitates the expansion of aged MSCs.…”

“…Additionally, oxygen consumption and ATP production were improved and the differentiation agenda into osteogenic, adipogenic and chondrogenic lineages was kept. 8 A recent in vitro report argued that the same 808-nm irradiation with higher power (1 W) and fluence (60 J/cm 2 ) for 60 s, repeated daily for four different time points, changed the MSC differentiation schedule of murine MSC. Indeed, providing the therapy with a flat-top hand-piece in continuous wave (CW) mode on an area of ~1 cm 2 increased the production of osteogenic runt-box-related transcription factor (Runx2) and osterix and slightly decreased the adipogenic protein peroxisome proliferator-activated receptor gamma (PPARγ), driving these cells to an osteogenic bias.…”

“…These findings suggest that pertinent laser therapy re-establishes mitochondrial respiration and facilitates the expansion of aged MSCs. 8 …”

“…6 Photobiomodulation therapy (PBM-t) has been indicated as very promising support for MSC handling, able to enhance the young MSC secretome or rejuvenate aged MSCs. 7,8 Moreover, PBM-t can interact with cellular photoacceptors in the mitochondria via different light parameters and modulate cell metabolism. 9 In this way, PBM-t may modify differently the MSC bias, prompting these cells towards a complete homeostatic reorganisation.…”