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人脐带间充质干细胞胶原支架显著改善大鼠模型中的宫腔粘连。

Collagen Scaffold with Human Umbilical Cord Mesenchymal Stem Cells Remarkably Improves Intrauterine Adhesions in a Rat Model.

机构信息

Dongguan Institute of Reproduction and Genetics, Dongguan Maternal and Children Health Hospital, Dongguan, China,

Dongguan Institute of Reproduction and Genetics, Dongguan Maternal and Children Health Hospital, Dongguan, China.

出版信息

Gynecol Obstet Invest. 2020;85(3):267-276. doi: 10.1159/000505691. Epub 2020 Apr 14.

Abstract

BACKGROUND

Intrauterine adhesion (IUA) is the second leading cause of secondary infertility in women. Research has shown that stem cells can promote endometrial regeneration and that biomaterials are also helpful in tissue regeneration. Therefore, we compared the efficacy of a collagen scaffold combined with either human umbilical cord mesenchymal stem cells (hUCMSC) or estrogen for the treatment of IUA.

METHODS

The IUA-induced rats were injected with hUCMSCs or estrogen, and with a collagen scaffold. The endometrial glands and amount of fibrosis were assessed using hematoxylin and eosin and Masson staining. The extent of fibrosis and levels of regeneration-related cytokines were examined by real-time quantitative PCR, and the expression levels of the estrogen receptor, KI67 and cytokeratin were analyzed using an immunochemistry assay. In addition, human nuclear antigen (HuNu) and vimentin were examined by immunofluorescence microscopy.

RESULTS

The collagen scaffold administered with hUCMSCs markedly increased the number of endometrial glands and reduced the area of fibrosis compared with either the collagen scaffold or hUCMSCs alone. In addition, the collagen scaffold with hUCMSCs significantly regulated the expression levels of fibrosis, estrogen, and differentiation-related genes relative to the collagen scaffold or hUCMSCs alone. Furthermore, the hUCMSCs alone or in combination with the collagen scaffold increased the expression of HuNu and vimentin in the IUA-induced rat model. In addition, protein levels of the p-transcriptional co-activator with PDZ-binding motif, stromal cell-derived factor-1, and C-X-C chemokine receptor type 4 were upregulated in the group that received the collagen scaffold in combination with -hUCMSCs.

CONCLUSION

Our results suggest that the combination of the collagen scaffold with hUCMSCs may be an alternative approach for treating IUA.

摘要

背景

宫腔粘连(IUA)是女性继发性不孕的第二大主要原因。研究表明,干细胞可以促进子宫内膜再生,生物材料也有助于组织再生。因此,我们比较了胶原蛋白支架联合人脐带间充质干细胞(hUCMSC)或雌激素治疗 IUA 的疗效。

方法

用 hUCMSC 或雌激素和胶原蛋白支架注射诱导 IUA 的大鼠。用苏木精和伊红及 Masson 染色评估子宫内膜腺体和纤维化程度。通过实时定量 PCR 检查纤维化程度和再生相关细胞因子水平,并通过免疫化学检测分析雌激素受体、Ki67 和细胞角蛋白的表达水平。此外,通过免疫荧光显微镜检查人核抗原(HuNu)和波形蛋白。

结果

与单独使用胶原蛋白支架或 hUCMSC 相比,胶原蛋白支架联合 hUCMSC 可显著增加子宫内膜腺体数量并减少纤维化面积。此外,与单独使用胶原蛋白支架或 hUCMSC 相比,胶原蛋白支架联合 hUCMSC 可显著调节纤维化、雌激素和分化相关基因的表达水平。此外,单独使用 hUCMSC 或联合胶原蛋白支架可增加 IUA 诱导大鼠模型中 HuNu 和波形蛋白的表达。此外,在联合使用 hUCMSC 的胶原蛋白支架组中,p-转录共激活因子与 PDZ 结合基序、基质细胞衍生因子-1 和 C-X-C 趋化因子受体 4 的蛋白水平上调。

结论

我们的结果表明,胶原蛋白支架联合 hUCMSC 可能是治疗 IUA 的一种替代方法。

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