中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (31): 6782-6791.doi: 10.12307/2025.660

• 干细胞综述 stem cell review • 上一篇    下一篇

间充质干细胞及细胞外囊泡修复子宫内膜损伤

熊正花1，2，周江洪2，沈  怡2，韩雪松2   

  1. 1昆明医科大学第一附属医院妇科，云南省昆明市  650032；2昆明医科大学附属延安医院/昆明市延安医院妇科，云南省昆明市  650051
  • 收稿日期:2024-07-04 接受日期:2024-08-12 出版日期:2025-11-08 发布日期:2025-02-27
  • 通讯作者: 韩雪松，博士，主任医师，教授，博士生导师，昆明医科大学附属延安医院/昆明市延安医院妇科，云南省昆明市 650051
  • 作者简介:熊正花，女，1992年生，普米族，昆明医科大学在读博士，主要从事干细胞治疗妇科疾病的研究。
  • 基金资助:
    国家自然科学基金项目(81960269)，项目负责人：韩雪松；云南省“万人计划”名医专项(RLHXS20210331)，项目负责人：韩雪松；云南省医学领军人才培养计划项目(L-2019005)，项目负责人：韩雪松；云南省科技厅-昆明医科大学联合专项重点项目(202401AY070001-374)，项目负责人：韩雪松；云南省教育厅科学研究基金项目(2024Y242)，项目负责人：熊正花

Mesenchymal stem cells and extracellular vesicles in repair of endometrial injury

Xiong Zhenghua1, 2, Zhou Jianghong2, Shen Yi2, Han Xuesong2   

  1. 1Department of Gynecology of First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China; 2Department of Gynecology of Yan’an Hospital Affiliated to Kunming Medical University/Yan’an Hospital of Kunming City, Kunming 650051, Yunnan Province, China
  • Received:2024-07-04 Accepted:2024-08-12 Online:2025-11-08 Published:2025-02-27
  • Contact: Han Xuesong, MD, Chief physician, Professor, Doctoral supervisor, Department of Gynecology of Yan’an Hospital Affiliated to Kunming Medical University/Yan’an Hospital of Kunming City, Kunming 650051, Yunnan Province, China
  • About author:Xiong Zhenghua, Doctoral candidate, Department of Gynecology of First Affiliated Hospital of Kunming Medical University, Kunming 650032, Yunnan Province, China; Department of Gynecology of Yan’an Hospital Affiliated to Kunming Medical University/Yan’an Hospital of Kunming City, Kunming 650051, Yunnan Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 81960269 (to HXS); Yunnan Province “Ten Thousand People Plan” Famous Doctor Special Project, No. RLHXS20210331 (to HXS); Yunnan Province Medical Leadership Talent Training Program Project, No. L-2019005 (to HXS); Special Key Project of Yunnan Provincial Science and Technology Department-Kunming Medical University Joint, No. 202401AY070001-374 (to HXS); Scientific Research Fund Project of Yunnan Provincial Education Department, No. 2024Y242 (to XZH)

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摘要：

文题释义：

间充质干细胞：是一类具有多向分化潜能的成体干细胞，能在特定条件下分化为多种细胞类型，如成骨细胞、软骨细胞、子宫内膜基质细胞等，还能分泌多种生长因子和细胞因子，在组织损伤修复中具有重要的调节作用。
子宫内膜损伤：指宫腔操作、炎症、感染等各种原因引起的子宫内膜基底层损伤，进而导致子宫腔部分或全部粘连，又称为Asherman综合征或子宫内膜过薄，患者主要表现为月经量少、不孕，子宫内膜纤维化是主要的病理改变。

摘要
背景：子宫内膜损伤是育龄期女性常见的良性疾病，严重影响女性的生育和生殖健康。近年来，间充质干细胞及其分泌的细胞外囊泡作为一种新的治疗策略，在子宫内膜损伤修复中备受关注。
目的：综述间充质干细胞及其细胞外囊泡在子宫内膜损伤治疗中的应用，全面介绍子宫内膜损伤的发病机制、治疗效果，探讨间充质干细胞及细胞外囊泡治疗子宫内膜损伤的潜力与挑战，以期为进一步的基础和临床研究提供理论依据。
方法：检索中国知网和中华医学全文数据库的中文文献，检索词为“间充质干细胞，间充质干细胞来源细胞外囊泡，外泌体，子宫内膜损伤，宫腔粘连，Asherman综合征”；检索PubMed数据库中的英文文献，英文检索词为“mesenchymal stem cells，extracellular vesicles derived from mesenchymal stem cells，exosome，endometrial injury，intrauterine adhesion，Asherman’s syndrome”，通过人工阅读的方法，排除重复文献或与子宫内膜损伤不相关的文献，最终纳入87篇文献。

结果与结论：间充质干细胞及其细胞外囊泡能够通过多种分子机制参与子宫内膜损伤的修复，如抗纤维化、促进血管生成和细胞增殖、细胞归巢、免疫调节、内膜容受性调节等，细胞和动物实验已取得大量研究成果，临床研究的初步结果也取得了一定的疗效，包括增加子宫内膜厚度、改善月经量和生育能力。但是，间充质干细胞及其细胞外囊泡治疗子宫内膜损伤的应用研究仍面临着困难和挑战。在治疗过程中，需要进一步提高间充质干细胞及其细胞外囊泡的质量和稳定性，明确其在细胞增殖、迁移、分化等过程中的调控作用。此外，还需开展大规模、多中心的临床试验，以验证间充质干细胞及其细胞外囊泡在子宫内膜损伤修复中的长期安全性和有效性，并确定最佳的治疗剂量和给药途径。随着科学技术的进步和生物工程材料的辅助应用，未来有望解决上述难题，开发出疗效更好、安全性更高的治疗手段。

https://orcid.org/0009-0003-1987-0890(熊正花)；https://orcid.org/0009-0001-9975-9062(韩雪松)


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: 干细胞, 间充质干细胞, 细胞外囊泡, 旁分泌, 宫腔粘连, 子宫内膜, 组织修复, 工程化干细胞, 工程化细胞外囊泡

Abstract: BACKGROUND: Endometrial injury is a common benign disease in women of reproductive age, which seriously affects their fertility and reproductive health. In recent years, mesenchymal stem cells and their secreted extracellular vesicles, as a new therapeutic strategy, have received much attention in the repair of endometrial injury.
OBJECTIVE: To review the application of mesenchymal stem cells and their secreted extracellular vesicles in the treatment of endometrial injury, to comprehensively understand the therapeutic mechanism and efficacy of endometrial injury, and to discuss the potential and challenges of the application of mesenchymal stem cells and their secreted extracellular vesicles in the treatment of endometrial injury, in order to provide theoretical basis for further basic and clinical research. 
METHODS: Literature searches were conducted in the China National Knowledge Infrastructure (CNKI), Chinese Medical Full-text Database, and PubMed electronic databases using search terms “mesenchymal stem cells, extracellular vesicles derived from mesenchymal stem cells, exosome, endometrial injury, intrauterine adhesion, Asherman’s syndrome” in Chinese and English. Articles were selected through manual screening to exclude duplicates and irrelevant studies, resulting in the inclusion of 87 articles.  
RESULTS AND CONCLUSION: Mesenchymal stem cells and their secreted extracellular vesicles can participate in endometrial damage repair through a variety of molecular mechanisms, such as anti-fibrosis, promoting angiogenesis and cell proliferation, cell homing, immune regulation, and endometrial receptibility regulation. A large number of research results have been achieved in cell and animal experiments, and preliminary results of clinical studies have also achieved certain curative effects, including increased endometrial thickness, improved menstrual volume and fertility. However, difficulty and challenges persist in the application of mesenchymal stem cells and their secreted extracellular vesicles for endometrial injury treatment. During treatment, it is necessary to enhance the quality and stability of mesenchymal stem cells and their secreted extracellular vesicles, as well as clarifying their roles in processes such as cell proliferation, migration, and differentiation. Moreover, large-scale multicenter clinical trials are needed to validate the long-term safety and efficacy of mesenchymal stem cells and their secreted extracellular vesicles in endometrial repair, and to determine optimal dosages and administration routes. Continuous advancements in scientific technologies and the auxiliary application of bioengineering materials offer hope for developing more effective and safer therapeutic methods for endometrial injury treatment and the above problems will be solved in the future.  


Key words: stem cell, mesenchymal stem cell, extracellular vesicle, paracrine, intrauterine adhesion, endometrium, tissue repair, engineered stem cell, engineered extracellular vesicle

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