Abstract
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.
Highlights
The majority of studies confirm that non-ionization and non-invasive methods with cell-therapy would affect skin tissue injury
By day 5, all radiated areas displayed the acute effects of moderate erythema, mildly dry skin, and hair loss
The results of this study indicated that the degree of acute radiation damage in groups treated with Adipose-derived mesenchymal stem cells (AdMSCs) was decreased
Summary
The majority of studies confirm that non-ionization and non-invasive methods with cell-therapy would affect skin tissue injury. The idea of using interventional methods with allogeneic stem cells in skin damage is one of the most important issues in radiation-induced injury in regenerative m edicine[6]. The presence, migration, proliferation, and differentiation of mesenchymal stem cells in the treated tissue may provide a promising therapeutic approach to improve radiation-induced skin tissue injury[7,8,9]. Apart from the importance of secretory factors in cellular and intercellular processes, the use of biological or mechanical stimuli are very significant for regulation and acceleration of growth and differentiation, migration into injured tissues, and better utilization of allogeneic connectivity in therapeutic cell applications, especially stem cells[10,11]. The main idea behind the use of low-intensity ultrasound in the medical field is the reconstruction of radiation injuries as a non-ionization m ethod[12]
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