人羊膜上皮细胞移植促进大鼠子宫瘢痕模型的形态和功能再生。
Transplantation of human amniotic epithelial cells promotes morphological and functional regeneration in a rat uterine scar model.
机构信息
International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, 200030, China.
Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, 200030, China.
出版信息
Stem Cell Res Ther. 2021 Mar 24;12(1):207. doi: 10.1186/s13287-021-02260-6.
BACKGROUND
Cesarean scar defect (CSD) is characterized by the presence of fibrotic tissue and decreased muscular density which is induced by cesarean section. Serious CSD may eventually result in infertility or obstetrical complications. Human amniotic epithelial cells (hAECs) have shown great promise in tissue regeneration. This study aims to investigate whether hAEC transplantation has the therapeutic effects on the rat uterine scar following full-thickness injury.
METHODS
A rat uterine scar model was established by excising the full-thickness uterine wall of about 1.0 cm in length and 1/2-2/3 of the total circumference in width. At day 30 post-surgery, hAECs were transplanted into the uterine scar. At day 30 and 60 post-transplantation, hematoxylin and eosin (H&E) staining, Masson staining, and IHC staining for vWF, VEGFA, α-SMA, and MMP-8 were performed to evaluate the regeneration of the scarred uterus and the underlying mechanism. Pregnancy outcomes were assessed at day 60 after hAEC transplantation. Finally, hAECs were incubated with hydrogen peroxide to verify the paracrine effect of hAECs.
RESULTS
Collagen deposition, thin myometrium, and injured endometrium were observed in the rat uterine scar model. After hAEC transplantation, collagen deposition in the uterine scar decreased, and myometrial and endometrial recovery was facilitated. hAEC transplantation also increased the fetus number implanted within the scarred area. Moreover, we found hAECs promoted angiogenesis via upregulation of VEGFA and decreased collagen deposition by upregulating MMP-8 in the uterine scar. The in vitro studies further demonstrated an increase in the expression level of MMP-8 in hAECs cultured with hydrogen peroxide.
CONCLUSIONS
These results suggested that hAEC transplantation may be efficacious in the functional repair and collagen degradation of uterine scars, which provides a new therapeutic strategy to CSD.
背景
剖宫产术后瘢痕缺陷（CSD）的特征是存在纤维化组织和肌肉密度降低，这是剖宫产引起的。严重的 CSD 最终可能导致不孕或产科并发症。人羊膜上皮细胞（hAEC）在组织再生方面显示出巨大的潜力。本研究旨在探讨 hAEC 移植对大鼠全层损伤子宫瘢痕的治疗作用。
方法
通过切除约 1.0cm 长、1/2-2/3 总周长宽的全层子宫壁，建立大鼠子宫瘢痕模型。术后 30 天，将 hAEC 移植到子宫瘢痕处。在移植后 30 天和 60 天，进行苏木精和伊红（H&E）染色、Masson 染色以及 vWF、VEGFA、α-SMA 和 MMP-8 的 IHC 染色，以评估瘢痕子宫的再生情况及其潜在机制。在 hAEC 移植后 60 天评估妊娠结局。最后，用双氧水孵育 hAEC，验证 hAEC 的旁分泌作用。
结果
在大鼠子宫瘢痕模型中观察到胶原沉积、薄型子宫肌层和损伤的子宫内膜。hAEC 移植后，子宫瘢痕中的胶原沉积减少，促进了子宫肌层和子宫内膜的恢复。hAEC 移植还增加了植入瘢痕区域的胎儿数量。此外，我们发现 hAEC 通过上调 VEGFA 促进血管生成，并通过上调 MMP-8 减少子宫瘢痕中的胶原沉积。体外研究进一步表明，hAEC 在培养于双氧水的条件下，MMP-8 的表达水平增加。
结论
这些结果表明，hAEC 移植可能对子宫瘢痕的功能修复和胶原降解有效，为 CSD 提供了一种新的治疗策略。
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