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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.
Highlights
The plasticity and proliferative capacity of stem cells decrease with aging, compromising their tissue regenerative potential and therapeutic applications
To further characterize the selected cell populations in terms of aging, the resulting BM-MSCssca1+, CD11b −, CD45 −, Pan DC − were subsequently analyzed for the expression of senescence and longevitypromoting markers by immunoblotting (Fig. 2)
Previous studies have shown that Sirtuin 1 (Sirt1) plays a critical role in longevity[42,43,44,45], and its expression and activity are decreased in aged cells, including MSCs46–48
Summary
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. Following the characterization of young and aged MSCs, our results show that a near-infrared PBM treatment delivering 3 J/cm[2] is the most effective modality for improving mitochondrial functionality and aging markers. 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. Stem cells exposed to NIR light exhibit increased proliferation[30,31] and have a greater mitochondrial membrane potential (MMP) and improved ATP generation[24,32], with effects being most prominent between 3 and 6 h after treatment[33]
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