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人羊膜间充质基质细胞移植可改善宫腔粘连啮齿动物模型中的子宫内膜再生。

Human amniotic mesenchymal stromal cell transplantation improves endometrial regeneration in rodent models of intrauterine adhesions.

作者信息

Gan Lu, Duan Hua, Xu Qian, Tang Yi-Qun, Li Jin-Jiao, Sun Fu-Qing, Wang Sha

机构信息

Department of Minimally Invasive Gynecologic Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

Department of Minimally Invasive Gynecologic Center, Beijing Obstetrics and Gynecology Hospital, Capital Medical University, Beijing, China.

出版信息

Cytotherapy. 2017 May;19(5):603-616. doi: 10.1016/j.jcyt.2017.02.003. Epub 2017 Mar 9.

DOI:10.1016/j.jcyt.2017.02.003
PMID:28285950
Abstract

BACKGROUND AIMS

Intrauterine adhesion (IUA) is a common uterine cavity disease characterized by the unsatisfactory regeneration of damaged endometria. Recently, stem cell transplantation has been proposed to promote the recovery process. Here we investigated whether human amniotic mesenchymal stromal cells (hAMSCs), a valuable resource for transplantation therapy, could improve endometrial regeneration in rodent IUA models.

METHODS

Forty female Sprague-Dawley rats were randomly assigned to five groups: normal, sham-operated, mechanical injury, hAMSC transplantation, and negative control group. One week after intervention and transplantation, histological analyses were performed, and immunofluorescent and immunohistochemical expression of cell-specific markers and messenger RNA expression of cytokines were measured.

RESULTS

Thicker endometria, increased gland numbers and fewer fibrotic areas were found in the hAMSC transplantation group compared with the mechanical injury group. Engraftment of hAMSCs was detected by the presence of anti-human nuclear antigen-positive cells in the endometrial glands of the transplantation uteri. Transplantation of hAMSCs significantly decreased messenger RNA levels of pro-inflammatory cytokines (tumor necrosis factor-α and interleukin-1β), and increased those of anti-inflammatory cytokines (basic fibroblast growth factor, and interleukin-6) compared with the injured uterine horns. Immunohistochemical expression of endometrial epithelial cells was revealed in specimens after hAMSC transplantation, whereas it was absent in the mechanically injured uteri.

CONCLUSIONS

hAMSC transplantation promotes endometrial regeneration after injury in IUA rat models, possibly due to immunomodulatory properties. These cells provide a more easily accessible source of stem cells for future research into the impact of cell transplantation on damaged endometria.

摘要

背景与目的

宫腔粘连(IUA)是一种常见的子宫腔疾病,其特征为受损子宫内膜再生不良。近来,有人提出进行干细胞移植以促进恢复过程。在此,我们研究了人羊膜间充质基质细胞(hAMSCs)这种移植治疗的宝贵资源,是否能改善啮齿动物IUA模型中的子宫内膜再生。

方法

40只雌性Sprague-Dawley大鼠被随机分为五组:正常组、假手术组、机械损伤组、hAMSC移植组和阴性对照组。干预和移植一周后,进行组织学分析,并检测细胞特异性标志物的免疫荧光和免疫组化表达以及细胞因子的信使RNA表达。

结果

与机械损伤组相比,hAMSC移植组的子宫内膜更厚,腺体数量增加,纤维化区域减少。通过移植子宫的子宫内膜腺体中存在抗人核抗原阳性细胞检测到hAMSCs的植入。与损伤的子宫角相比,hAMSCs移植显著降低了促炎细胞因子(肿瘤坏死因子-α和白细胞介素-1β)的信使RNA水平,并增加了抗炎细胞因子(碱性成纤维细胞生长因子和白细胞介素-6)的信使RNA水平。hAMSC移植后标本中显示出子宫内膜上皮细胞的免疫组化表达,而在机械损伤的子宫中则不存在。

结论

hAMSC移植可促进IUA大鼠模型损伤后的子宫内膜再生,可能是由于其免疫调节特性。这些细胞为未来研究细胞移植对受损子宫内膜的影响提供了更容易获取的干细胞来源。

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