Work

Fractional carbon dioxide laser-induced photothermal activation of mesenchymal stem cell-derived exosomes accelerates diabetic wound healing by enhancing angiogenesis

Year: 2026

Type: article

Abstract: BACKGROUND Exosomes (Exos) derived from mesenchymal stem cells (MSCs) have emerged as a promising therapeutic option for diabetic wound healing owing to their strong pro-angiogenic potential. Nevertheless, their relatively low bioactivity remains a major barrier to successful clinical application. Fractional CO2 laser therapy offers a precise and controllable form of photothermal stimulation that may potentiate exosome activity without the need for additional exogenous agents, possibly promoting more effective diabetic wound repair. AIM To investigate the mechanisms through which low-energy fractional Exos derived from CO2 laser-preconditioned adipose-derived MSCs (Ad-MSCs) (CO2 laser-Exos) promote the healing of diabetic wounds. METHODS Ad-MSCs were subjected to a single exposure of fractional CO2 laser at energy densities of 30 mJ/cm2, 40 mJ/cm2, or 50 mJ/cm2. Infrared thermography was employed to monitor temperature fluctuations in the culture medium. To determine the optimal energy level, western blotting was performed to assess heat shock protein 90 expression, while apoptosis was analyzed by flow cytometry. Exos were subsequently isolated through ultracentrifugation, and sphingosine-1-phosphate (S1P) concentrations within the Exos were measured using enzyme-linked immunosorbent assay. The therapeutic efficacy and underlying mechanisms of CO2 laser-Exos were further investigated through a series of in vitro and in vivo experiments. RESULTS Following a single exposure to fractional CO2 laser, the culture medium temperature increased rapidly and then gradually declined. Among the tested groups, Ad-MSCs treated with 40 mJ/cm2 demonstrated the highest heat shock protein 90 expression and exhibited reduced apoptosis. in vitro , CO2 laser-Exos markedly promoted the proliferation, migration, and tube formation of human umbilical vein endothelial cells, while their S1P content was higher than that of unconditioned Exos. Under high-glucose conditions, human umbilical vein endothelial cells showed increased expression of S1P receptor 1 (S1PR1). Silencing S1PR1 significantly impaired the pro-angiogenic activity of CO2 laser-Exos and suppressed the expression of phosphorylated protein kinase B, hypoxia-inducible factor 1 alpha, and vascular endothelial growth factor-A. In vivo , compared with Exos, CO2 laser-Exos substantially accelerated diabetic wound healing by promoting neovascularization within the wound bed. CONCLUSION Low-energy fractional CO2 laser irradiation augments the biological activity of MSC-derived Exos through photothermal stimulation. These Exos, in turn, enhance endothelial cell functions by activating the S1PR1/protein kinase B/hypoxia-inducible factor 1 alpha signaling pathway, ultimately accelerating the repair of diabetic wounds.

Source: World Journal of Diabetes

DOI: 10.4239/wjd.v17.i1.112942