军事医学2024，Vol.48Issue(5)：325-333,9.DOI:10.7644/j.issn.1674-9960.2024.05.002
基因修饰的干细胞外泌体水凝胶治疗放射性皮肤损伤的实验研究
Effects of hydrogel loaded with gene-modified stem cell exosomes on radioactive skin injury
摘要
Abstract
Objective To evaluate the therapeutic effect of poloxamer hydrogel loaded with exosomes derived from human dental pulp stem cells genetically modified with human hepatocyte growth factor against radiation skin injuries.Methods Human dental pulp stem cells derived exosomes(DPSC-Exo)and hepatocyte growth factor modified DPSC-Exo(HGF-DPSC-Exo)were extracted via ultracentrifugation separation,identified in terms of particle size and morphology,and analyzed separately by means of nanoparticle tracking analysis and scanning electron microscopy(SEM),while exosome marker proteins were determined by Western blot.Then,the effect of exosomes on radiation-damaged skin cells was assessed.The poloxamer hydrogel was prepared and its safety was evaluated with CCK-8.A mouse model of injury combined with radiation injury was established,and the therapeutic effect of hydrogel loaded with exosomes was determined based on wound size,HE and Masson staining.Furthermore,the underlining therapeutic mechanism was explored with Tunnel assay,malondialdehyde content and peroxidase activity.Results The diameter exosomes ranged from 30 to 150 nm and their morphology was a disc-shaped vesicle under SEM.Moreover,CD9,CD63 and TSG101 were expressed.The results of cellular experiments showed that exosomes significantly promoted the proliferation and migration of radiation-damaged skin keratinocytes and fibroblasts,and reduced their apoptosis.HGF modification enhanced the healing effect of exosomes.Poloxamer hydrogel showed good temperature-sensitive properties and biocompatibility.The results of animal experiments showed that exosomes significantly accelerated the healing of radiation-combined injuries in mice,inhibited inflammatory infiltration and mitigated collagen deposition in the wound.Interestingly,the healing effect in the group treated with hydrogel loaded with exosomes was the best.The underlining mechanism was possibly related to promotion of cell proliferation and inhibition of apoptosis and oxidative stress.Conclusion A novel poloxamer hydrogel loaded HGF-DPSC-Exo has been prepared and its therapeutic effect against radiation combined injury has been proved,thus providing a new strategy for the treatment of radiation skin injury in clinic.关键词
肝细胞生长因子/牙髓干细胞/外泌体/泊洛沙姆温敏水凝胶/放射性皮肤损伤Key words
human hepatocyte growth factor/dental pulp stem cells/exosomes/poloxamer temperature-sensitive hydrogel/radiation skin injury分类
医药卫生引用本文复制引用
任博媛,李强,靳嘉岩,王一晨,丁泓帆,靳继德..基因修饰的干细胞外泌体水凝胶治疗放射性皮肤损伤的实验研究[J].军事医学,2024,48(5):325-333,9.基金项目
军队后勤科研项目(JKAWS22J1005,AWS21J003) （JKAWS22J1005,AWS21J003）
