中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (1): 31-37.doi: 10.12307/2025.040

• 脂肪干细胞 adipose-derived stem cells • 上一篇    下一篇

脂肪间充质干细胞来源外泌体改善放射性口腔黏膜炎

李 杨,付丽丽,杨建堂   

  1. 遵义医科大学附属口腔医院,贵州省遵义市 563000
  • 收稿日期:2024-01-16 接受日期:2024-02-22 出版日期:2025-01-08 发布日期:2024-05-18
  • 通讯作者: 杨建堂,博士,副教授,遵义医科大学附属口腔医院,贵州省遵义市 563000
  • 作者简介:李杨,女,1982 年生,贵州省遵义市人,汉族,2010 年四川大学华西口腔医学院毕业,硕士,副主任医师,主要从事口腔黏膜病学及预防医学的研究。
  • 基金资助:
    国家自然科学基金项目 (81960202),项目负责人:杨建堂;贵州省科技厅项目 ( 黔科合基础 -ZK[2023] 一般 534), 项目负责人:杨建堂

Adipose mesenchymal stem cell-derived exosome attenuates radiation-induced oral mucositis

Li Yang, Fu Lili, Yang Jiantang   

  1. Affiliated Stomatological Hospital, Zunyi Medical University, Zunyi 563000, Guizhou Province, China
  • Received:2024-01-16 Accepted:2024-02-22 Online:2025-01-08 Published:2024-05-18
  • Contact: Yang Jiantang, MD, Associate professor, Affiliated Stomatological Hospital, Zunyi Medical University, Zunyi 563000, Guizhou Province, China
  • About author:Li Yang, Master, Associate chief physician, Affiliated Stomatological Hospital, Zunyi Medical University, Zunyi 563000, Guizhou Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 81960202 (to YJT); Guizhou Provincial Department of Science and Technology Project, No. ZK[2023]534 (to YJT)

摘要:

文题释义:

外泌体:是细胞通过旁分泌释放的具有特征性表面抗原的小囊泡,其直径范围为30-150 nm。外泌体通过转运DNA、RNA和蛋白质来调节 细胞间的相互作用,在多种疾病病理生理过程中发挥着重要作用。 

放射性口腔黏膜炎:头颈部恶性肿瘤约占全身恶性肿瘤的5%,其发病隐匿、易转移,放疗是其重要的治疗手段之一。但放疗极易引发口 腔黏膜炎症,发病率90%以上,轻者黏膜充血,严重者口腔黏膜大面积充血、糜烂及溃疡,难以进食,不仅影响患者的生存质量,而且会 影响肿瘤患者的治疗计划。 


背景:头颈肿瘤放疗极易引起放射性口腔黏膜炎,严重影响患者的健康及肿瘤的治疗计划。间充质干细胞在多种疾病中表现出治疗潜力, 外泌体是其发挥功能的重要因素之一。目前尚无脂肪间充质干细胞来源外泌体应用于放射性口腔黏膜炎的相关研究。 

目的:探讨脂肪间充质干细胞来源外泌体在放射性口腔黏膜炎中的作用。 

方法:提取脂肪间充质干细胞及脂肪间充质干细胞来源外泌体并进行鉴定。通过3 Gy X射线辐射口腔黏膜上皮细胞诱导放射性口腔黏膜炎 体外模型,在造模前给予脂肪间充质干细胞或脂肪间充质干细胞来源外泌体预处理48 h,EdU实验和克隆形成实验检测口腔黏膜上皮细胞 的增殖能力。通过3 Gy X射线辐射构建放射性口腔黏膜炎小鼠模型,将脂肪间充质干细胞和脂肪间充质干细胞来源外泌体分别注入放射性 口腔黏膜炎小鼠尾静脉,采用苏木精-伊红染色和免疫组化评估口腔黏膜上皮组织的炎症变化。

结果与结论:①与对照组相比,脂肪间充质干细胞及脂肪间充质干细胞来源外泌体均可促进口腔黏膜上皮细胞克隆形成,增加口腔黏膜上 皮细胞EdU阳性率;②脂肪间充质干细胞及脂肪间充质干细胞来源外泌体均能够缓解辐射处理小鼠口腔黏膜上皮组织的炎症;口腔黏膜上 皮组织中CD45阳性细胞均减少,PCNA阳性细胞均增加。结果表明,脂肪间充质干细胞来源外泌体可促进口腔黏膜上皮细胞增殖,对放射 性口腔黏膜炎小鼠口腔黏膜炎症具有缓解作用。

https://orcid.org/0000-0002-6285-7881 (李杨) 


中国组织工程研究杂志出版内容重点:干细胞;骨髓干细胞;造血干细胞;脂肪干细胞;肿瘤干细胞;胚胎干细胞;脐带脐血干细胞;干细胞诱导;干细胞分化;组织工程

关键词: 放射性口腔黏膜炎, 脂肪间充质干细胞, 外泌体, 头颈部肿瘤, 放疗, 口腔黏膜, 炎症, 恶性肿瘤

Abstract:

BACKGROUND: Radiotherapy for head and neck tumors is very likely to cause radiation-induced oral mucositis, which seriously affects the health of patients and the treatment plan of tumors. Mesenchymal stem cells have shown therapeutic potential in many diseases, and exosomes are one of the important factors for their function. At present, there is no application of adipose mesenchymal stem cell-derived exosomes in the study of radiation-induced oral mucositis. 

OBJECTIVE: To investigate the role of adipose mesenchymal stem cell-derived exosomes in radiation-induced oral mucositis. 

METHODS: Adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes were extracted and identified. In vitro model of radiationinduced oral mucositis was induced by radiating oral mucosal epithelial cells with 3 Gy X-ray. Adipose mesenchymal stem cells or adipose mesenchymal stem cell-derived exosomes were pretreated for 48 hours before modeling. The proliferation capacity of oral mucosal epithelial cells was detected by EdU assay and clonal formation assay. A mouse model of radiation-induced oral mucositis was constructed through 3 Gy X-ray radiation. Adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes were injected into the tail vein of radiation-induced oral mucositis mice. Hematoxylin-eosin staining and immunohistochemistry were used to evaluate the inflammatory changes of oral mucosal epithelial tissue. 

RESULTS AND CONCLUSION: (1) Compared with the control group, both adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes promoted the formation of oral epithelial cell clones and increased the positive rate of EdU in oral epithelial cells. (2) Both adipose mesenchymal stem cells and adipose mesenchymal stem cell-derived exosomes alleviated the inflammation of oral mucosal epithelium of irradiated mice; CD45 positive cells decreased and PCNA positive cells increased in oral mucosal epithelium. It is concluded that adipose mesenchymal stem cell-derived exosomes promote the proliferation of oral mucosal epithelial cells and release oral mucosal inflammation in mice with radiation-induced oral mucositis. 

Key words: radiation-induced oral mucositis, adipose-derived mesenchymal stem cell, exosome, head and neck tumor, radiation therapy, oral mucosa, inflammation, malignant tumor

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