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人羊膜间充质干细胞改善复发性自然流产小鼠的炎症浸润和妊娠结局。

The improvement of inflammatory infiltration and pregnancy outcome in mice with recurrent spontaneous abortion by human amniotic mesenchymal stem cells.

机构信息

Graduate School of China Medical University, Shenyang 110000, China.

School of Public Health, Fudan University, Shanghai 200000, China.

出版信息

Biol Reprod. 2024 Aug 15;111(2):351-360. doi: 10.1093/biolre/ioae074.

Abstract

Recurrent spontaneous abortion is thought to be mostly triggered by immune-related causes. Mesenchymal stem cells, which exhibit the traits of multi-directional differentiation capacity and low immunogenicity, have recently been recommended as a viable treatment for spontaneous abortion-prone mice to increase the success of pregnancy. Amniotic membrane tissue is a byproduct of pregnancy and delivery that has a wide range of potential uses due to its easy access to raw materials and little ethical constraints. To construct an abortion-prone mouse model for this investigation, CBA/J female mice were coupled with male DBA/2 mice, while CBA/J female mice were paired with male BALB/c mice as a control. The identical volume of human amniotic mesenchymal stem cells or phosphate buffer was injected intraperitoneally on the 4.5th day of pregnancy. CBA/J female mice were sacrificed by cervical dislocation on the 13.5th day of pregnancy, the embryo absorption rate was calculated, and the uterus, decidua tissues and placenta were gathered for examination. Through detection, it was discovered that human amniotic mesenchymal stem cells significantly increased the expression of interleukin 10 and transforming growth factor beta, while they significantly decreased the expression of interleukin 1 beta and interleukin 6, improved vascular formation and angiogenesis, and minimized the embryo absorption rate and inflammatory cell infiltration in the recurrent spontaneous abortion + human amniotic mesenchymal stem cells group. In any case, human amniotic mesenchymal stem cells regulate inflammatory factors and cell balance at the maternal-fetal interface, which result in a reduction in the rate of embryo absorption and inflammatory infiltration and provide an innovative perspective to the clinical therapy of recurrent spontaneous abortion.

摘要

复发性自然流产被认为主要是由免疫相关原因引起的。间充质干细胞具有多向分化能力和低免疫原性的特点,最近被推荐作为治疗易发生自然流产的小鼠的一种可行方法,以提高妊娠成功率。羊膜组织是妊娠和分娩的副产品,由于其原材料易得且伦理限制较少,具有广泛的潜在用途。为了构建这种研究用的易发生流产的小鼠模型,CBA/J 雌性小鼠与雄性 DBA/2 小鼠交配,而 CBA/J 雌性小鼠与雄性 BALB/c 小鼠交配作为对照。在妊娠第 4.5 天,通过腹腔内注射等量的人羊膜间充质干细胞或磷酸盐缓冲液。妊娠第 13.5 天,通过颈椎脱位处死 CBA/J 雌性小鼠,计算胚胎吸收率,并采集子宫、蜕膜组织和胎盘进行检查。通过检测发现,人羊膜间充质干细胞显著增加了白细胞介素 10 和转化生长因子 β 的表达,同时显著降低了白细胞介素 1β 和白细胞介素 6 的表达,改善了血管形成和血管生成,并最大限度地降低了复发性自然流产+人羊膜间充质干细胞组的胚胎吸收率和炎症细胞浸润。在任何情况下,人羊膜间充质干细胞调节母胎界面的炎症因子和细胞平衡,从而降低胚胎吸收率和炎症浸润率,为复发性自然流产的临床治疗提供了新的视角。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/c66f/11327314/15ea69b66dfc/ioae074ga1.jpg

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