Department of Obstetrics and Gynecology, National Clinical Research Center for Obstetric & Gynecologic Diseases, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Medical Science Research Center, State Key Laboratory of Complex Severe and Rare Diseases, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, China.
Stem Cell Res Ther. 2021 Jul 15;12(1):406. doi: 10.1186/s13287-021-02488-2.
Current surgical therapies for pelvic organ prolapse (POP) do not repair weak vaginal tissue and just provide support; these therapies may trigger severe complications. Stem cell-based regenerative therapy, due to its ability to reconstruct damaged tissue, may be a promising therapeutic strategy for POP. The objective of this study is to evaluate whether mesenchymal stem cell (MSC) therapy can repair weak vaginal tissue in an ovariectomized rhesus macaque model.
A bilateral ovariectomy model was established in rhesus macaques to induce menopause-related vaginal injury. Ten bilaterally ovariectomized rhesus macaques were divided into two groups (n=5/group): the saline group and the MSC group. Three months after ovariectomy, saline or MSCs were injected in situ into the injured vaginal wall. The vaginal tissue was harvested 12 weeks after injection for histological and biochemical analyses to evaluate changes of extracellular matrix, microvascular density, and smooth muscle in the vaginal tissue. Biomechanical properties of the vaginal tissue were assessed by uniaxial tensile testing. Data analysis was performed with unpaired Student's t test or Mann-Whitney.
Twelve weeks after MSC transplantation, histological and biochemical analyses revealed that the content of collagen I, elastin, and microvascular density in the lamina propria of the vagina increased significantly in the MSC group compared with the saline group. And the fraction of smooth muscle in the muscularis of vagina increased significantly in the MSC group. In addition, MSC transplantation improved the biomechanical properties of the vagina by enhancing the elastic modulus.
Vaginal MSC transplantation could repair the weak vaginal tissue by promoting extracellular matrix ingrowth, neovascularization, and smooth muscle formation and improve the biomechanical properties of the vagina, providing a new prospective treatment for POP.
目前治疗盆腔器官脱垂(POP)的手术疗法并不能修复薄弱的阴道组织,而只是提供支撑;这些疗法可能会引发严重的并发症。基于干细胞的再生疗法因其能够重建受损组织,可能是治疗 POP 的一种有前途的治疗策略。本研究旨在评估间充质干细胞(MSC)疗法是否可以修复去卵巢恒河猴模型中薄弱的阴道组织。
建立恒河猴双侧卵巢切除术模型,以诱导与绝经相关的阴道损伤。10 只双侧去卵巢恒河猴分为两组(n=5/组):生理盐水组和 MSC 组。去卵巢 3 个月后,将生理盐水或 MSC 原位注射到损伤的阴道壁中。注射后 12 周采集阴道组织进行组织学和生化分析,以评估阴道组织中细胞外基质、微血管密度和平滑肌的变化。通过单轴拉伸试验评估阴道组织的生物力学特性。数据分析采用配对 Student's t 检验或 Mann-Whitney 检验。
MSC 移植后 12 周,组织学和生化分析显示 MSC 组阴道固有层中 I 型胶原、弹性蛋白和微血管密度的含量明显高于生理盐水组。并且 MSC 组阴道肌层中的平滑肌比例明显增加。此外,MSC 移植通过增强弹性模量改善了阴道的生物力学特性。
阴道 MSC 移植可通过促进细胞外基质的生长、血管新生和平滑肌形成来修复薄弱的阴道组织,并改善阴道的生物力学特性,为 POP 提供了一种新的有前途的治疗方法。