Low-intensity ultrasound combined with allogenic adipose-derived mesenchymal stem cells (AdMSCs) in radiation-induced skin injury treatment

Mesenchymal stem cells are mechano-sensitive cells with the potential to restore the function of damaged tissues. Low-intensity ultrasound has been increasingly considered as a bioactive therapeutic apparatus. Optimizing transplantation conditions is a critical aim for radiation-induced skin tissue injury. Therefore, the therapeutic function of adipose-derived mesenchymal stem cells to ultrasound stimulus was examined based on the mechanical index (MI). Mesenchymal stem cells were isolated from the adipose tissues of mature guinea pigs. An ultrasound system (US) was constructed with a 40 kHz frequency. The radiation-induced skin injury model was produced on the abdominal skin of guinea pigs by 60 Gy of radiation. Then, they were divided to 7 groups (n=42): control, sham, US (MI=0.7), AdMSCs injection, US AdMSCs (AdMSCs, under US with MI=0.2), AdMSCs+US (AdMSCs transplantation and US with MI=0.7) and US AdMSCs+US (combining the last two groups). The homing of stem cells was verified with fluorescence imaging. The groups were followed with serial photography, ultrasound imaging, tensiometry, and histology. The thickness of the skin was analyzed. Functional changes in skin tissue were evaluated with Young's modulus (kPa). One-way ANOVA tests were performed to analyze differences between treatment protocols (p<0.05). The results of Kumar's score showed that radiation injury was significantly lower in the treatment groups of US AdMSCs and US AdMSCs+US than other groups after 14 days (p<0.05). There was a significant difference in skin thickness between treatment groups with control, sham, and US groups after 60 Gy radiation and were closer to the thickness of healthy skin. Young's modulus in US AdMSCs+US, US AdMSCs, and AdMSCs+US groups demonstrated a significant difference with the other groups (p<0.05). Young's modulus in US AdMSCs+US and US AdMSCs treatment groups were closer to Young's modulus of the healthy skin. The histological results confirmed the improvement of acute radiation damage in the combined treatment method, especially in US AdMSCs+US and US AdMSCs groups with increasing the epithelialization and formation of collagen. An ultrasonic treatment plan based on a mechanical index of the target medium could be used to enhance stem cell therapy.