中国组织工程研究

中国组织工程研究 ›› 2026, Vol. 30 ›› Issue (1): 1-9.doi: 10.12307/2025.575

• 骨髓干细胞 bone marrow stem cells •    下一篇

不同鼠龄骨髓间充质干细胞来源外泌体保护放射性肺损伤

张婷婷1，李亚龙2，岳浩迪1，李颜君1，耿熙炆1，张玉薇1，刘小转1   

  1. 1河南省人民医院临床单细胞生物医学中心，郑州大学人民医院，河南省郑州市   450000；2河南省人民医院干细胞研究中心，河南省干细胞临床应用与关键技术重点实验室，郑州大学人民医院，河南省郑州市   450000 
  • 收稿日期:2024-11-22 接受日期:2025-03-04 出版日期:2026-01-08 发布日期:2025-06-11
  • 通讯作者: 刘小转，博士，副研究员，河南省人民医院临床单细胞生物医学中心，郑州大学人民医院，河南省郑州市 450000
  • 作者简介:张婷婷，女，1990年生，河南省郑州市人，硕士，助理研究员，主要从事干细胞及外泌体相关的基础研究。
  • 基金资助:
    河南省自然科学基金青年基金项目(232300421297)，项目负责人：张婷婷；河南省重点研发与推广专项(232102311040)，项目负责人：李亚龙；河南省卫生计生科技英才海外研修项目(HWYX2019133)，项目负责人：刘小转

Protection of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury

Zhang Tingting1, Li Yalong2, Yue Haodi1, Li Yanjun1, Geng Xiwen1, Zhang Yuwei1, Liu Xiaozhuan1   

  1. 1Center for Clinical Single-Cell Biomedicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China; 2Stem Cell Research Center, Henan Provincial People’s Hospital, Henan Key Laboratory of Stem Cell Clinical Application and Key Technology, People’s Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
  • Received:2024-11-22 Accepted:2025-03-04 Online:2026-01-08 Published:2025-06-11
  • Contact: Liu Xiaozhuan, MD, Associate research fellow, Center for Clinical Single-Cell Biomedicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
  • About author:Zhang Tingting, MS, Assistant research fellow, Center for Clinical Single-Cell Biomedicine, Henan Provincial People’s Hospital, People’s Hospital of Zhengzhou University, Zhengzhou 450000, Henan Province, China
  • Supported by:
    Natural Science Foundation of Henan Province (Youth Program), No. 232300421297 (to ZTT); Key Research & Development and Promotion Project of Henan Province, No. 232102311040 (to LYL); Overseas Training Program of Henan Province (Health Science and Technology Talents), No. HWYX2019133 (to LXZ)

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摘要：


文题释义：

骨髓间充质干细胞：是在哺乳动物骨髓基质中发现的具有自我增殖和多向分化潜能(成骨、成脂、成软骨分化等)的干细胞，主要通过旁分泌方式介导组织修复，对多种疾病具有治疗潜力。
外泌体：是由细胞释放的具有双层脂质膜的小囊泡，携带来源于亲本细胞的多种内容物(蛋白质、脂类、miRNA等)，也是干细胞发挥旁分泌作用的重要因子之一。


背景：间充质干细胞通过递送外泌体对放射性肺损伤具有巨大的治疗潜力，而年龄是影响间充质干细胞功能和生物疗效的主要因素之一。

目的：探究不同鼠龄骨髓间充质干细胞来源外泌体对小鼠放射性肺损伤的保护作用。
方法：采用全骨髓贴壁培养法获得青年小鼠骨髓间充质干细胞和老年小鼠骨髓间充质干细胞，从第3代骨髓间充质干细胞上清液中分离出外泌体。随机取10只2月龄C57BL/6J小鼠进行假照射作为对照组，剩余30只2月龄C57BL/6J小鼠建立放射性肺损伤模型，随机分为3组，分别经尾静脉注射青年小鼠骨髓间充质干细胞来源外泌体、老年小鼠骨髓间充质干细胞来源外泌体和PBS，观察各组小鼠存活率，在照射后第1，12周检测肺功能、肺组织炎症和纤维化情况。
结果与结论：①青年小鼠骨髓间充质干细胞来源外泌体的颗粒物和蛋白质浓度高于老年小鼠骨髓间充质干细胞来源外泌体；②与对照组相比，PBS组小鼠存活率低，照射后第1周肺组织炎症明显，白细胞介素1β、白细胞介素6、肿瘤坏死因子α水平及mRNA表达升高；照射后第12周肺组织内胶原沉积，E-钙黏蛋白mRNA水平降低，而α-平滑肌肌动蛋白、转化生长因子β1和β-连环蛋白mRNA表达升高；③与PBS组相比，外泌体组小鼠存活率显著提高，照射后第1周促炎因子水平及mRNA表达降低，照射后第12周E-钙黏蛋白mRNA表达升高，α-平滑肌肌动蛋白、转化生长因子β1和β-连环蛋白mRNA表达降低；④上述所有指标中，青年小鼠骨髓间充质干细胞来源外泌体的疗效均优于老年小鼠骨髓间充质干细胞来源外泌体；⑤结果表明，青年小鼠骨髓间充质干细胞来源外泌体含有更多颗粒物和蛋白质，对小鼠放射性肺损伤早期炎症和晚期纤维化的缓解效果优于老年小鼠骨髓间充质干细胞来源外泌体。

关键词: 放射性肺损伤, 青年, 老年, 骨髓间充质干细胞, 外泌体, 炎症, 纤维化, 工程化外泌体

Abstract: BACKGROUND: Mesenchymal stem cells show extremely therapeutic potential for radiation-induced lung injury through delivering exosomes. Age is a primary factor affecting the function and biological efficacy of mesenchymal stem cells.
OBJECTIVE: To investigate the protective effects of exosomes derived from bone marrow mesenchymal stem cells of different mouse ages on radiation-induced lung injury in mice.  
METHODS: Bone marrow mesenchymal stem cells of young mice and old mice were obtained by whole bone marrow adherent culture. The exosomes were isolated from the supernatant of passage 3 bone marrow mesenchymal stem cells. Ten 2-month-old C57BL/6J mice were randomly selected as the control group after anesthesia and not irradiated. The remaining 30 2-month-old C57BL/6J mice were used to establish a mouse radiation-induced lung injury model and were randomly divided into three groups. Exosomes derived from bone marrow mesenchymal stem cells of young mice, exosomes derived from bone marrow mesenchymal stem cells of old mice, and PBS were injected through the tail vein, respectively. The survival rate of mice was monitored. The lung function, lung inflammation and fibrosis were assessed at 1 and 12 weeks after irradiation.
RESULTS AND CONCLUSION: (1) The concentrations of particles and proteins in exosomes derived from bone marrow mesenchymal stem cells of young mice were higher than those in exosomes derived from bone marrow mesenchymal stem cells of old mice. (2) Compared with the control group, the survival rate of mice in the PBS group was low, and lung inflammation was obvious at week 1 after irradiation, and the levels and mRNA expressions of interleukin-1β, interleukin-6, and tumor necrosis factor-α were increased. Collagen deposition in lung tissues was observed at week 12 after irradiation, and the mRNA level of E-cadherin was decreased, while the mRNA levels of α-smooth muscle actin, transforming growth factor-β1, and β-catenin were increased. (3) Compared with the PBS group, the survival rate of mice in the exosome group was significantly improved, and the level of proinflammatory factors and their mRNA expression were reduced at week 1 after irradiation, the mRNA level of E-cadherin was increased, and the mRNA levels of α-smooth muscle actin, transforming growth factor β1 and β-catenin were reduced at week 12 after irradiation. (4) Among all the above indicators, the therapeutic effect of exosomes derived from bone marrow mesenchymal stem cells of young mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice. (5) The results showed that exosomes derived from bone marrow mesenchymal stem cells of young mice contained more particles and proteins, and the effect of alleviating early inflammation and late fibrosis of radiation-induced lung injury in mice was better than that of exosomes derived from bone marrow mesenchymal stem cells of old mice.


Key words: radiation-induced lung injury, young, aged, bone marrow mesenchymal stem cell, exosome, inflammation, fibrosis, engineered exosome

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