中国组织工程研究

中国组织工程研究 ›› 2025, Vol. 29 ›› Issue (31): 6792-6799.doi: 10.12307/2025.552

• 干细胞综述 stem cell review • 上一篇    下一篇

围产期间充质干细胞及联合水凝胶治疗宫腔粘连的作用和机制

钟  敏1，2，王  成2，3，范振海1，2，李林艳1，2，余丽梅2，3，4   

  1. 遵义医科大学附属医院，1妇产科(产前诊断中心)，2贵州省生物制造实验室，3贵州省细胞工程中心，贵州省遵义市   563003；4遵义医科大学教育部省部共建组织损伤修复与再生医学协同创新中心，贵州省遵义市   563003
  • 收稿日期:2024-08-15 接受日期:2024-09-23 出版日期:2025-11-08 发布日期:2025-02-27
  • 通讯作者: 余丽梅，博士，二级教授，博导，遵义医科大学附属医院，贵州省生物制造实验室，贵州省细胞工程中心，贵州省遵义市 563003；遵义医科大学教育部省部共建组织损伤修复与再生医学协同创新中心，贵州省遵义市 563003
  • 作者简介:钟敏，女，1993年生，贵州省织金县人，彝族，遵义医科大学在读硕士，主要从事生殖疾病与再生医学研究。
  • 基金资助:
    国家自然科学基金项目(82060270)，项目负责人：余丽梅；遵义市大数据与科技局市院联合基金基础项目[遵市科合HZ字(2023)282号]，项目负责人：李林艳

Effect and mechanism of perinatal mesenchymal stem cells and their combination with hydrogels in treatment of intrauterine adhesions

Zhong Min1, 2, Wang Cheng2, 3, Fan Zhenhai1, 2, Li Linyan1, 2, Yu Limei2, 3, 4   

  1. 1Department of Obstetrics and Gynecology (Prenatal Diagnostic Center), 2Guizhou Province Biofabrication Laboratory, 3Guizhou Province Center of Cell Engineering, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China; 4Collaborative Innovation Center of Tissue Damage Repair and Regenerative Medicine of Ministry of Education, Zunyi Medical University, Zunyi 563003, Guizhou Province, China
  • Received:2024-08-15 Accepted:2024-09-23 Online:2025-11-08 Published:2025-02-27
  • Contact: Yu Limei, MD, Professor, Doctoral supervisor, Guizhou Province Biofabrication Laboratory, and Guizhou Province Center of Cell Engineering, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China; Collaborative Innovation Center of Tissue Damage Repair and Regenerative Medicine of Ministry of Education, Zunyi Medical University, Zunyi 563003, Guizhou Province, China
  • About author:Zhong Min, Master candidate, Department of Obstetrics and Gynecology (Prenatal Diagnostic Center), and Guizhou Province Biofabrication Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi 563003, Guizhou Province, China
  • Supported by:
    National Natural Science Foundation of China, No. 82060270 (to YLM); Zunyi Big Data and Science and Technology Bureau Municipal Institute Joint Fund Basic Project, No. [Zunyi Science and Technology Bureau HZ (2023) 282] (to LLY)

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摘要：

文题释义：

宫腔粘连：是指宫内手术、感染等所致的子宫内膜基底层损伤，导致子宫内膜干/祖细胞缺失，子宫内膜修复异常，内膜纤维化，最终引起各宫壁间相互粘连的病理状态。
围产期间充质干细胞：是一类贴壁生长且具有分化能力的成体干细胞，主要源于胎儿娩出时的脐带、羊膜、胎盘、脐血，具有来源丰富、可塑性强、低免疫原性等优点，表达间质细胞及干细胞特异标记分子，具有分泌、免疫调节等多种功能活性。
水凝胶：主要由凝胶单体交联形成的三维空间网状结构，为细胞黏附、迁移、增殖分化等提供支撑，可负载生长因子，为移植细胞提供适宜的环境。

摘要
背景：中、重度宫腔粘连的临床治疗效果差，粘连分离术后复发率高，严重影响育龄期女性的生殖健康，是临床亟需解决的难题。围产期间充质干细胞及其联合水凝胶的应用具有独特的优势，它们在宫腔粘连方面的治疗作用尤其受到关注。
目的：总结围产期间充质干细胞及其联合水凝胶治疗宫腔粘连的研究进展。
方法：以“间充质干细胞，围产期，水凝胶，宫腔粘连，子宫内膜损伤”为中文检索词，以“mesenchymal stem cells, perinatal period, hydrogel, intrauterine adhesions, endometrium injury”为英文检索词，检索2010-2024年发表的相关文献，检索数据库包括PubMed、中国知网及万方数据库，对80篇符合入组标准的文献进行综述分析。
结果与结论：①与其他来源间充质干细胞相似，围产期间充质干细胞对宫腔粘连具有良好治疗作用，可满足自体或异体移植。②移植的细胞来源于脐带、羊膜、胎盘和脐血，这些围产期间充质干细胞移植治疗宫腔粘连的作用和机制涉及定植分化、细胞免疫、旁分泌作用，及促进内膜再生与血管新生、抗内膜细胞凋亡、抑制上皮间质化、抗纤维化及调节相关信号通路。③围产期间充质干细胞联合水凝胶在宫腔粘连的治疗中具有协同效应，在间充质干细胞效应基础上，水凝胶还发挥了支撑及维持间充质干细胞持续释放、促进细胞迁移、黏附等作用，有助于更好地促进子宫内膜再生和抗纤维化，有利于修复受损的子宫内膜，提高子宫内膜容受性和生育力，降低复发率。④已有少量临床试验初步验证了脐带间充质干细胞、水凝胶治疗宫腔粘连的有效性和安全性，尚需深入研究围产期间充质干细胞与水凝胶等高分子生物材料的相互作用，及其联合应用治疗宫腔粘连的其他作用和分子机制。

关键词: 干细胞, 间充质干细胞, 围产期, 水凝胶, 宫腔粘连, 薄型子宫内膜, 纤维化, 工程化干细胞

Abstract: BACKGROUND: The therapeutic efficacy of moderate or severe intrauterine adhesions is poor. After synechotomy, the high postoperative recurrence rate severely affects the reproductive health of women of childbearing age, which is an urgent problem to be solved in clinical practice. Perinatal mesenchymal stem cells and their combined hydrogels have unique advantages, and they have received particular attention on the treatment of intrauterine adhesions. 
OBJECTIVE: To summarize the research progress of perinatal mesenchymal stem cells and their combined hydrogel in the treatment of intrauterine adhesions.
METHODS: Search terms were “mesenchymal stem cells, perinatal period, hydrogel, intrauterine adhesions, endometrial injury” in Chinese and English. Relative articles published from 2010 to 2024 were retrieved on PubMed, CNKI, and WanFang databases. As a result, 80 articles that met the inclusion criteria were reviewed and analyzed. 
RESULTS AND CONCLUSION: (1) Similar to other sources of mesenchymal stem cells, perinatal mesenchymal stem cells have a good therapeutic effect on intrauterine adhesions, and can meet the needs of autologous and allogeneic transplantation. (2) The mechanism of perinatal mesenchymal stem cell transplantation from umbilical cord, amniotic membrane, placenta, and umbilical cord blood in the treatment of uterine adhesion involves in regulation of relative signaling pathways such as colonization and differentiation, cellular immunity, paracrine, and promoting endometrial regeneration and angiogenesis, immune regulation, anti-endometrial cell apoptosis, inhibition of epithelial-mesenchymal transition, and anti-fibrosis. (3) Perinatal mesenchymal stem cells combined with hydrogel have a synergistic effect on the treatment of intrauterine adhesions. On the basis of the effect of mesenchymal stem cells, the hydrogel also plays a role in supporting and maintaining the continuous release of mesenchymal stem cells, promoting cell migration and adhesion, which is helpful to better promote endometrial regeneration and anti-fibrosis. It is beneficial to repair the damaged endometrial, improve endometrial receptivity and fertility, and reduce the recurrence rate. (4) A few of clinical trials have initially verified the effectiveness and safety of umbilical cord mesenchymal stem cells or hydrogels in the treatment of intrauterine adhesions. Further studies are still needed on the interaction between perinatal mesenchymal stem cells and polymer biomaterials such as hydrogels, and other effects and molecular mechanism of combined treatment of intrauterine adhesions. 


Key words: stem cell, mesenchymal stem cell, perinatal period, hydrogel, intrauterine adhesion, thin endometrium, fibrosis, engineered stem cell

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