Key Takeaways & Executive Findings
- •• Both normoxic and hypoxic preconditioned human amniotic mesenchymal stem cell exosomes significantly improved the proliferation of radiation-injured submandibular gland epithelial cells. • Treatment with exosomes increased α-amylase secretion and aquaporin 5 mRNA expression in radiation-injured cells, indicating functional recovery. • Hypoxic preconditioning of exosomes did not confer a statistically significant advantage over normoxic exosomes in repairing radiation damage. • Exosomes derived from human amniotic mesenchymal stem cells may serve as a potential cell-free therapy for radiation-induced salivary gland injury.
Abstract
BACKGROUND: Hypoxia preconditioning can increase extracellular vesicles, growth factors, anti-inflammatory and immunosuppressive factors in the parasecretory secretions of mesenchymal stem cells. Exosomes derived from human amniotic mesenchymal stem cells preconditioned with hypoxia are expected to play a better therapeutic role in tissue damage repair. OBJECTIVE: To observe the repair effect of exosomes from human amniotic mesenchymal stem cells preconditioned with hypoxia on radiation-induced submandibular gland epithelial cell damage. METHODS: The passage 3 human amniotic mesenchymal stem cells were divided into two groups: hypoxia and normoxia. They were pretreated with hypoxia (1% O2 by volume) and normoxia (20% O2 by volume) for 48 hours, respectively. Then, normoxic and hypoxic human amniotic mesenchymal stem cell exosomes were extracted from the culture supernatant of human amniotic mesenchymal stem cells by modified ultrahigh-speed centrifugation. The submandibular gland epithelial cells of SD newborn rats were divided into blank control group, radiation control group, normoxia-treated group, and hypoxia-treated group. The submandibular gland epithelial cells were treated with 5 Gy radiation to construct a radiation-induced injury model. The normoxia-treated and hypoxia-treated groups were co-cultured with normoxic or hypoxic exosomes for 3 days. CCK-8 assay was used to detect the proliferation activity of rat submandibular gland epithelial cells; ELISA was used to measure the content of α-amylase in the supernatant; RT-qPCR was used to detect the expression of aquaporin 5 mRNA. RESULTS AND CONCLUSION: The cell proliferation activity in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The cell proliferation activity in the normoxia-treated and hypoxia-treated groups on days 2 and 3 was significantly higher than that in the radiation control group (P < 0.05). The cell proliferation activity in the hypoxia-treated group on day 1 was higher than that in the normoxia-treated group, and showed an increasing trend on days 2 and 3, but there was no statistical difference compared with the normoxia-treated group (P > 0.05). The α-amylase content in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The α-amylase content in the normoxia-treated and hypoxia-treated groups was significantly higher than that in the radiation control group (P < 0.05). Compared with the normoxia-treated group, the α-amylase content in the hypoxia-treated group showed an increasing trend, but there was no statistical difference (P > 0.05). The expression of aquaporin 5 mRNA in the radiation control group was significantly lower than that in the blank control group (P < 0.05). The expression of aquaporin 5 mRNA in the normoxia-treated and hypoxia-treated groups was significantly higher than that in the radiation control group (P < 0.05). The expression of aquaporin 5 mRNA in the hypoxia-treated group was slightly higher than that in the normoxia-treated group, but there was no statistical difference (P > 0.05). The results indicate that both normoxic and hypoxic preconditioned human amniotic mesenchymal stem cell exosomes have a repair effect on radiation-induced submandibular gland epithelial cell damage, but hypoxic exosomes have no obvious advantage.
1. Introduction
Radiotherapy for head and neck malignant tumors often leads to damage of salivary gland epithelial cells, resulting in degeneration and atrophy of acinar cells, reduced secretion, and abnormal secretion of electrolytes and proteins. Approximately 40% of patients develop xerostomia [1-2], which severely affects their quality of life. Currently, there is no effective treatment for radiation-induced salivary gland injury [3-4]. Studies have shown that mesenchymal stem cells can promote tissue repair and regeneration by modulating immune responses, inhibiting inflammatory responses, and secreting cytokines [3]. In recent years, biological therapies such as local stem cell transplantation have made some progress in the field of radiation-induced salivary gland injury [2,5], but there are limitations such as insufficient stem cell sources, immunogenicity, teratogenicity, and carcinogenicity, which restrict clinical application [6].
Human amniotic mesenchymal stem cells (hAMSCs) have good proliferative capacity and stem cell characteristics, making them suitable for regenerative repair of ischemic tissue damage (e.g., wound healing) [7-12]. Our previous studies found that hypoxia-preconditioned hAMSCs can more effectively repair radiation-damaged salivary gland function [13-15], and this mechanism is related to the paracrine effects of hAMSCs [16-17]. In this study, a 5 Gy radiation-induced submandibular gland epithelial cell injury model was established, and the cells were co-cultured with normoxic and hypoxic preconditioned hAMSC-derived exosomes to observe their repair effects.
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Zhang Ligang, Liu Tao, Yi Jie, Zhang Nini, Yao Li, Huang Guilin, Hu Xiaohua, Dai Min (2026). Function of human amniotic mesenchymal stem cell exosomes in repairing submandibular gland epithelial cells after radiation injury in SD rats. Chinese Journal of Tissue Engineering Research. https://doi.org/10.12307/2026.21207
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Frequently Asked Questions
What is the main finding of this study?
The study found that both normoxic and hypoxic preconditioned human amniotic mesenchymal stem cell exosomes can repair radiation-induced submandibular gland epithelial cell damage, but hypoxic exosomes do not show a significant advantage over normoxic exosomes.
How were the exosomes derived?
Exosomes were extracted from the culture supernatant of human amniotic mesenchymal stem cells (passage 3) using modified ultrahigh-speed centrifugation, after preconditioning with either hypoxia (1% O2) or normoxia (20% O2) for 48 hours.
What methods were used to assess the repair effect?
The repair effect was assessed using CCK-8 assay for cell proliferation, ELISA for α-amylase secretion, and RT-qPCR for aquaporin 5 mRNA expression.
What is the clinical significance of this research?
This research suggests that human amniotic mesenchymal stem cell exosomes could be a potential cell-free therapy for radiation-induced salivary gland injury, which is a common side effect of radiotherapy for head and neck cancers.
Did hypoxia preconditioning enhance the therapeutic effect of exosomes?
No, the study found no statistically significant difference between hypoxic and normoxic exosomes in terms of cell proliferation, α-amylase secretion, or aquaporin 5 mRNA expression, indicating that hypoxia preconditioning did not provide an obvious advantage.
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