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脂肪来源间充质干细胞治疗实验性阿舍曼综合征诱导的大鼠。

Adipose derived mesenchymal stem cell treatment in experimental asherman syndrome induced rats.

机构信息

Department of Histology and Embryology, School of Medicine, Pamukkale University, Pamukkale, Denizli, Turkey.

Department of Medical Biology, School of Medicine, Pamukkale University, Pamukkale, Denizli, Turkey.

出版信息

Mol Biol Rep. 2020 Jun;47(6):4541-4552. doi: 10.1007/s11033-020-05505-4. Epub 2020 May 22.

DOI:10.1007/s11033-020-05505-4
PMID:32444974
Abstract

Asherman syndrome (AS) occurs due to fibrosis or uterine adhesions as a result of damage to the basal layer of the endometrium. The aim of this study is investigating the effects of adipose tissue-derived mesenchymal stem cell (ADMSC) application on the expression of vascular endothelial growth factor (VEGF), insulin-like growth factor (IGF-1), miRNA-98, miRNA199a in endometrial tissue in rats with AS. Study groups were designed as, control (C), Asherman syndrome (AS), AS + oral estrogen (ASO), AS + ADMSC (ASSC), AS + oral estrogen + ADMSC (ASSCO) with 7 samples in each group. Characterization and differentiation experiments were performed in ADMSC obtained. Two weeks after the development of the AS, ADMSC therapy was applied. BrdU (5-bromo-2'-deoxyuridine) labeling was performed to show the presence of ADMSC in the tissues. Rats were sacrificed after 8 weeks and bilateral uterine horn resection was performed. Tissues were fixed in formaldehyde. After routine tissue follow-up, sections were taken and evaluated with hematoxylin eosin staining. VEGF1 and IGF1 expressions were evaluated by immunohistochemical staining and western blot analysis. Expression changes of miR-98 and miR-199a were detected by RT-PCR. Our results showed that stem cells and estrogen giving together reduced inflammation and fibrosis in the endometrium. Immunohistochemistry and western blot results suggested that this effect was achieved especially through IGF-1. In our study, decreased miR-98 and miR-199a expressions were determined in Asherman syndrome. Furthermore, no changes of miRNA expressions were observed in treatment groups.

摘要

Asherman 综合征(AS)是由于子宫内膜基底层损伤导致纤维化或子宫粘连而发生的。本研究旨在探讨脂肪组织来源的间充质干细胞(ADMSC)应用对 AS 大鼠子宫内膜组织中血管内皮生长因子(VEGF)、胰岛素样生长因子(IGF-1)、miRNA-98、miRNA199a 表达的影响。研究组设计为对照组(C)、Asherman 综合征组(AS)、AS 加口服雌激素组(ASO)、AS 加 ADMSC 组(ASSC)、AS 加口服雌激素加 ADMSC 组(ASSCO),每组 7 只。对获得的 ADMSC 进行了鉴定和分化实验。在 AS 形成后 2 周进行 ADMSC 治疗。BrdU(5-溴-2'-脱氧尿苷)标记显示 ADMSC 存在于组织中。8 周后处死大鼠,切除双侧子宫角。组织用甲醛固定。常规组织随访后,取组织切片,用苏木精-伊红染色进行评估。用免疫组织化学染色和 Western blot 分析评估 VEGF1 和 IGF1 的表达。通过 RT-PCR 检测 miR-98 和 miR-199a 的表达变化。我们的结果表明,干细胞和雌激素联合使用可减少子宫内膜的炎症和纤维化。免疫组化和 Western blot 结果表明,这种作用主要是通过 IGF-1 实现的。在我们的研究中,在 Asherman 综合征中确定了 miR-98 和 miR-199a 的表达降低。此外,治疗组未观察到 miRNA 表达的变化。

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本文引用的文献

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Hyaluronic Acid Hydrogel Integrated with Mesenchymal Stem Cell-Secretome to Treat Endometrial Injury in a Rat Model of Asherman's Syndrome.透明质酸水凝胶与间充质干细胞分泌组联合治疗宫腔粘连综合征大鼠模型的子宫内膜损伤。
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Human Adipose Derived Stem Cells Exhibit Enhanced Liver Regeneration in Acute Liver Injury by Controlled Releasing Hepatocyte Growth Factor.人脂肪来源干细胞通过可控释放肝细胞生长因子在急性肝损伤中表现出增强的肝脏再生能力。
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Bone Marrow Mesenchymal Stem Cells (BMSCs) Restore Functional Endometrium in the Rat Model for Severe Asherman Syndrome.
脂肪来源间充质干细胞负载胶原子宫内膜贴片对薄型子宫内膜大鼠子宫内膜再生的影响。
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Stem cells implanted with nanofibrous mats for injured endometrial regeneration and immune-microenvironment remodeling.将干细胞与纳米纤维垫一起植入,用于受损子宫内膜的再生和免疫微环境重塑。
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Exploring the future potential of mesenchymal stem/stromal cells and their derivatives to support assisted reproductive technology for female infertility applications.探讨间充质干细胞及其衍生细胞在支持女性不孕不育应用的辅助生殖技术方面的未来潜力。
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Bone Marrow-Derived Stem Cell (BMDSC) transplantation improves fertility in a murine model of Asherman's syndrome.骨髓源性干细胞(BMDSC)移植可改善阿谢曼综合征小鼠模型的生育能力。
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Transplantation of bone marrow mesenchymal stem cells on collagen scaffolds for the functional regeneration of injured rat uterus.胶原支架骨髓间充质干细胞移植促进大鼠损伤子宫功能重建。
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