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脂肪来源间充质干细胞接种的脱细胞羊膜移植于大鼠宫腔粘连模型

Transplantation of acellular amniotic membrane seeded with adipose-derived mesenchymal stem cells in a rat model of intrauterine adhesion.

作者信息

Li Chunbo, Yao Liangfeng, He Fengquan, Hua Keqin

机构信息

Department of Obstetrics and Gynecology, The Obstetrics & Gynecology Hospital of Fudan University, Shanghai.

Department of Obstetrics and Gynecology, Zhangzhou Municipal Hospital of Fujian Province, Zhangzhou.

出版信息

Ann Med Surg (Lond). 2024 Jul 1;86(8):4463-4474. doi: 10.1097/MS9.0000000000002249. eCollection 2024 Aug.

DOI:10.1097/MS9.0000000000002249
PMID:39118771
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11305806/
Abstract

OBJECTIVE

This study aimed to investigate the role of acellular amniotic membrane (AAM) loaded with adipose-derived mesenchymal stem cells (ADSCs) for the treatment of intrauterine adhesion.

METHODS

One hundred twenty female Spargue-Dawley rats were randomly divided into four groups: sham operation group (the uterus was picked out and incised without treatment), intrauterine adhesion group, the experimental group treated with AAM, and experimental group treated with AAM loaded with ADSCs. Histological and immunohistochemical analysis were performed on 3, 7, and 14 days after surgery to evaluate the degree of uterine fibrosis and regeneration of injured endometrium. RNA sequencing and real-time PCR were used to explore the potential mechanism by which ADSCs modulated immune response and promoted endometrial regeneration.

RESULTS

On 14 days after surgery, the endometrial thickness, number of glands, and degree of fibrosis reduction in the ADSCs/AAM group was higher than those in the AAM group, and similar to the sham operation group. RNA sequencing analysis showed that ADSCs can modulate local immune responses and promote the formation of functional endometrium. Meanwhile, we found that ADSCs significantly decreased the levels of pro-inflammatory cytokines (TNF-α and IL-1β) and increased the levels of anti-inflammatory cytokines (bFGF and IL-6).

CONCLUSION

Our results demonstrated that AAM loaded with ADSCs can result in the regeneration of injured endometrium and fibrosis reduction. Meanwhile, ADSCs also regulated the immune microenvironment, which was beneficial to functional endometrial recovery.

摘要

目的

本研究旨在探讨负载脂肪间充质干细胞(ADSCs)的脱细胞羊膜(AAM)在治疗宫腔粘连中的作用。

方法

将120只雌性斯普拉格-道利大鼠随机分为四组:假手术组(仅取出子宫并切开,不做处理)、宫腔粘连组、AAM治疗实验组、负载ADSCs的AAM治疗实验组。术后3天、7天和14天进行组织学和免疫组化分析,以评估子宫纤维化程度和受损子宫内膜的再生情况。采用RNA测序和实时定量PCR技术,探索ADSCs调节免疫反应和促进子宫内膜再生的潜在机制。

结果

术后14天,ADSCs/AAM组的子宫内膜厚度、腺体数量及纤维化减轻程度均高于AAM组,与假手术组相似。RNA测序分析表明,ADSCs可调节局部免疫反应,促进功能性子宫内膜形成。同时,我们发现ADSCs显著降低促炎细胞因子(TNF-α和IL-1β)水平,提高抗炎细胞因子(bFGF和IL-6)水平。

结论

我们的结果表明,负载ADSCs的AAM可促进受损子宫内膜再生并减轻纤维化。同时,ADSCs还可调节免疫微环境,有利于功能性子宫内膜恢复。

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