Photobiomodulation preconditioned diabetic adipose derived stem cells with additional photobiomodulation: an additive approach for enhanced wound healing in diabetic rats with a delayed healing wound

In this preclinical investigation, we examined the effects of combining preconditioned diabetic adipose-derived mesenchymal stem cells (AD-MSCs) and photobiomodulation (PBM) on a model of infected ischemic delayed healing wound (injury), (IIDHWM) in rats with type I diabetes (TIDM). During the stages of wound healing, we examined multiple elements such as stereology, macrophage polarization, and the mRNA expression levels of stromal cell-derived factor (SDF)-1α, vascular endothelial growth factor (VEGF), hypoxia-induced factor 1α (HIF-1α), and basic fibroblast growth factor (bFGF) to evaluate proliferation and inflammation. The rats were grouped into: (1) control group; (2) diabetic-stem cells were transversed into the injury site; (3) diabetic-stem cells were transversed into the injury site then the injury site exposed to PBM; (4) diabetic stem cells were preconditioned with PBM and implanted into the wound; (5) diabetic stem cells were preconditioned with PBM and transferred into the injury site, then the injury site exposed additional PBM. While on both days 4, and 8, there were advanced histological consequences in groups 2–5 than in group 1, we found better results in groups 3–5 than in group 2 (p < 0.05). M1 macrophages in groups 2–5 were lower than in group 1, while groups 3–5 were reduced than in group 2 (p < 0.01). M2 macrophages in groups 2–5 were greater than in group 1, and groups 3–5 were greater than in group 2. (p ≤ 0.001). Groups 2–5 revealed greater expression levels of bFGF, VEGF, SDF- 1α, and HIF‐ 1α genes than in group 1 (p < 0.001). Overall group 5 had the best results for histology (p < 0.05), and macrophage polarization (p < 0.001). AD-MSC, PBM, and AD-MSC + PBM treatments all enhanced the proliferative stage of injury repairing in the IIDHWM in TIDM rats. While AD-MSC + PBM was well than the single use of AD-MSC or PBM, the best results were achieved with PBM preconditioned AD-MSC, plus additional PBM of the injury.