Huang Shuangying, Cheng Chunxia, Wang Zhibiao, Li Ruizhen, Li Waixing, Yu Kenan, Shi Qiuling, Xue Min
State Key Laboratory of Ultrasound in Medicine and Engineering, College of Biomedical Engineering, Chongqing Medical University, Chongqing, China.; Department of Obstetrics, The Third Xiangya Hospital of Central South University, Changsha, China.
Department of Obstetrics, The Third Xiangya Hospital of Central South University, Changsha, China.
Reprod Biomed Online. 2025 Mar;50(3):104486. doi: 10.1016/j.rbmo.2024.104486. Epub 2024 Oct 16.
What is the effect and underlying mechanism of low-intensity-pulsed-ultrasound (LIPUS)-treated menstrual-blood-derived mesenchymal stem cells (MenSC) on intrauterine adhesions (IUA)?
First, MenSC were identified and exposed to LIPUS. The proliferation, migration, invasion, cytokine secretion, and ability to differentiate into human endometrial epithelial cells (HEEC) of LIPUS-treated MenSC were characterized. In vitro, human endometrial stromal cells (HESC) were treated with 10 ng/ml transforming growth factor-β1 (TGF-β1) to simulate IUA, and then co-cultured indirectly with LIPUS-treated MenSC. In vivo, IUA rat models were constructed and LIPUS-treated MenSC were transplanted into the uterus. The morphology, structure, and levels of fibrosis and repair-related factors of the uterus were detected. In the mechanism study, insulin-like growth factor-1 (IGF-1) was applied to verify whether the PI3K/AKT pathway participated in the repair of endometrial injury by LIPUS-treated MenSC.
In vitro, LIPUS treatment showed beneficial effects on MenSC by promoting cell proliferation and migration; inhibiting apoptosis; and enhancing the expression of epidermal growth factor, hepatocyte growth factor and vascular endothelial growth factor. It also facilitated the differentiation of MenSC into HEEC while reducing the level of fibrosis in TGF-β1-treated HESC by decreasing the concentrations of p-PI3K and p-AKT. However, these effects were reversed with the use of IGF-1. In vivo, transplantation of LIPUS-treated MenSC resulted in increased uterine length, width and weight. The transplanted cells also improved completeness of the endometrial structure, reduced inflammatory infiltration, increased endometrial thickness and gland abundance, and decreased endometrial fibrosis. Additionally, increased concentations of endometrial-repair-related proteins and receptivity-related markers were observed after transplantation of LIPUS-treated MenSC.
LIPUS-treated MenSC repaired endometrial injury by inhibiting the PI3K/AKT pathway.
低强度脉冲超声（LIPUS）处理的月经血源性间充质干细胞（MenSC）对宫腔粘连（IUA）的影响及潜在机制是什么？
首先，鉴定MenSC并使其暴露于LIPUS。对LIPUS处理的MenSC的增殖、迁移、侵袭、细胞因子分泌以及分化为人子宫内膜上皮细胞（HEEC）的能力进行表征。在体外，用人子宫内膜基质细胞（HESC）与10 ng/ml转化生长因子-β1（TGF-β1）共同处理以模拟IUA，然后与LIPUS处理的MenSC间接共培养。在体内，构建IUA大鼠模型并将LIPUS处理的MenSC移植到子宫中。检测子宫的形态、结构以及纤维化和修复相关因子的水平。在机制研究中，应用胰岛素样生长因子-1（IGF-1）来验证PI3K/AKT通路是否参与LIPUS处理的MenSC对子宫内膜损伤的修复。
在体外，LIPUS处理通过促进细胞增殖和迁移、抑制细胞凋亡以及增强表皮生长因子、肝细胞生长因子和血管内皮生长因子的表达，对MenSC产生有益影响。它还促进MenSC分化为HEEC，同时通过降低p-PI3K和p-AKT的浓度来降低TGF-β1处理的HESC中的纤维化水平。然而，使用IGF-1后这些作用被逆转。在体内，LIPUS处理的MenSC移植导致子宫长度、宽度和重量增加。移植的细胞还改善了子宫内膜结构的完整性，减少了炎症浸润，增加了子宫内膜厚度和腺体丰度，并减少了子宫内膜纤维化。此外，在LIPUS处理的MenSC移植后，观察到子宫内膜修复相关蛋白和接受性相关标志物的浓度增加。
LIPUS处理的MenSC通过抑制PI3K/AKT通路修复子宫内膜损伤。
