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人去细胞羊膜基质联合预先种植的脐带间充质干细胞在大鼠损伤模型中恢复子宫内膜功能。

Human Acellular Amniotic Matrix with Previously Seeded Umbilical Cord Mesenchymal Stem Cells Restores Endometrial Function in a Rat Model of Injury.

机构信息

Peking University People's Hospital, Reproductive Medicine Center, Beijing 100044, China.

Beijing Friendship Hospital, Capital Medical University, Department of Obstetrics and Gynecology, Beijing 100050, China.

出版信息

Mediators Inflamm. 2021 Sep 3;2021:5573594. doi: 10.1155/2021/5573594. eCollection 2021.

DOI:10.1155/2021/5573594
PMID:34531703
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8438588/
Abstract

BACKGROUND

Abnormal endometrial repair after injury results in the formation of intrauterine adhesions (IUA) and a thin endometrium, which are key causes for implantation failure and infertility. Stem cell transplantation offers a potential alternative for some cases of severe Asherman's syndrome that cannot be treated with surgery or hormonal therapy. Umbilical cord-derived mesenchymal stem cells (UCMSCs) have been reported to repair the damaged endometrium. However, there is no report on the effects of UCMSCs previously seeded on human acellular amniotic matrix (AAM) on endometrial injury.

METHODS

Absolute ethanol was injected into rat uteri to damage the endometrium. UCMSCs previously seeded on AAM were surgically transplanted. Using a variety of methods, the treatment response was assessed by endometrial thickness, endometrial biomarker expression, endometrial receptivity, cell proliferation, and inflammatory factors.

RESULTS

Endometrial thickness was markedly improved after UCMSC-AAM transplantation. The expression of endometrial biomarkers, namely, vimentin, cytokeratin, and integrin 3, in treated rats increased compared with untreated rats. In the UCMSC-AAM group, the VEGF expression decreased, whereas that of MMP9 increased compared with the injury group. Moreover, in the AAM group, the MMP9 expression increased. The expression of proinflammatory factors (IL-2, TNF, and IFN-) in the UCMSC-AAM group decreased compared with the untreated group, whereas the expression of anti-inflammatory factors (IL-4, IL-10) increased significantly.

CONCLUSIONS

UCMSC transplantation using AAM as the carrier can be applied to treat endometrial injury in rats. The successful preparation of lyophilized AAM provides the possibility of secondary infectious disease screening and amniotic matrix quality detection, followed by retrospective analysis. The UCMSC-AAM complex may promote the better application of UCMSCs on the treatment of injured endometrium.

摘要

背景

损伤后子宫内膜修复异常会导致宫腔粘连(IUA)和薄型子宫内膜的形成,这是着床失败和不孕的主要原因。干细胞移植为一些无法通过手术或激素治疗的严重 Asherman 综合征病例提供了一种潜在的替代方法。已经有报道称脐带间充质干细胞(UCMSCs)可修复受损的子宫内膜。然而,目前尚无关于预先接种在人去细胞羊膜基质(AAM)上的 UCMSCs 对子宫内膜损伤的影响的报道。

方法

向大鼠子宫内注射无水乙醇以损伤子宫内膜。手术移植预先接种在 AAM 上的 UCMSCs。通过多种方法,通过子宫内膜厚度、子宫内膜生物标志物表达、子宫内膜容受性、细胞增殖和炎症因子来评估治疗反应。

结果

UCMSC-AAM 移植后子宫内膜厚度明显改善。与未治疗组相比,治疗组大鼠子宫内膜生物标志物波形蛋白、细胞角蛋白和整合素 3 的表达增加。在 UCMSC-AAM 组中,VEGF 表达降低,而 MMP9 表达增加。此外,在 AAM 组中,MMP9 的表达增加。与未治疗组相比,UCMSC-AAM 组促炎因子(IL-2、TNF 和 IFN-)的表达减少,而抗炎因子(IL-4、IL-10)的表达显著增加。

结论

以 AAM 为载体的 UCMSC 移植可应用于治疗大鼠子宫内膜损伤。冻干 AAM 的成功制备为二次传染病筛查和羊膜基质质量检测提供了可能性,随后进行回顾性分析。UCMSC-AAM 复合物可能促进 UCMSCs 更好地应用于治疗受损的子宫内膜。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d2/8438588/1991c1926d7d/MI2021-5573594.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d2/8438588/f007e4097e93/MI2021-5573594.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d2/8438588/e8f0a1f29f6b/MI2021-5573594.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d2/8438588/1991c1926d7d/MI2021-5573594.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d2/8438588/f007e4097e93/MI2021-5573594.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d2/8438588/e8f0a1f29f6b/MI2021-5573594.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/01d2/8438588/1991c1926d7d/MI2021-5573594.003.jpg

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