Umbilical cord-derived mesenchymal stem cells secretomes promote embryo development and implantation

IF 5.2 2区医学 Q1 MEDICINE, RESEARCH & EXPERIMENTAL

Life sciences Pub Date : 2025-05-08 DOI:10.1016/j.lfs.2025.123693

Prompunya Teerapong , Yuan-Ting Yang , Dilip Bhargava Sreerangaraja Urs , Jun-Jen Liu , Shu-Huei Kao

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引用次数: 0

Abstract

Aims

Successful implantation relies on high-quality blastocysts, uterine receptivity, and effective embryo-endometrium communication. This study investigated the effects of umbilical cord-derived mesenchymal stem cells (UC-MSC) secretomes on embryo development and implantation.

Main methods

Trophoblastic spheroids and murine embryos were used to evaluate the impact of UC-MSC secretomes. Embryos obtained through superovulation were cultured in vitro and divided into five groups: a control group and four experimental groups treated with varying concentrations of UC-MSC secretomes (2.5, 5, 10, and 50 μg/mL). Embryo development competence and implantation potential were assessed in each group, and the expression levels of related genes were analyzed.

Key findings

Supplementation with UC-MSC secretomes significantly enhanced trophoblast cell migration. It also stimulated endometrial cell proliferation and upregulated key implantation-related genes (LIF, LIFR, VEGFA, ITGB3, and ITGAV), improving endometrial receptivity and adhesion in trophoblastic spheroid co-cultures. While morulation rates of murine embryos remained unchanged, UC-MSC secretomes supplement significantly increased blastulation, pluripotency gene expression, and hatching rates. Supplementation with 10 and 50 μg/mL significantly increased blastocyst diameter and blastomere number, as well as embryo adhesion, outgrowth areas, and implantation rates. Additionally, growth factor analysis showed elevated VEGF-A and PDGF-AA levels in the culture media.

Significance

This study demonstrates that UC-MSC secretomes enhance both embryo development and endometrial cell function, facilitating implantation potential. These findings suggest their potential utility in supporting preimplantation embryos and improving maternal endometrial receptivity in ART.

Abstract Image

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脐带源性间充质干细胞分泌组促进胚胎发育和着床

目的成功着床依赖于高质量囊胚、子宫容受性和有效的胚胎-子宫内膜沟通。本研究探讨了脐带间充质干细胞（UC-MSC）分泌组对胚胎发育和着床的影响。主要方法采用滋养球型细胞和小鼠胚胎评价UC-MSC分泌组的影响。通过超排卵获得的胚胎体外培养，分为5组：对照组和4个实验组，分别用不同浓度的UC-MSC分泌组（2.5、5、10和50 μg/mL）处理。评估各组胚胎发育能力和着床潜能，分析相关基因表达水平。补充UC-MSC分泌组显著增强滋养细胞迁移。它还能刺激子宫内膜细胞增殖，上调关键的植入相关基因（LIF、LIFR、VEGFA、ITGB3和ITGAV），改善滋养层球体共培养中子宫内膜的容受性和粘附性。在小鼠胚胎模拟率保持不变的情况下，UC-MSC分泌组的补充显著提高了囊胚率、多能性基因表达和孵化率。添加10和50 μg/mL可显著增加囊胚直径和囊胚数量，增加胚胎黏附、外生面积和着床率。此外，生长因子分析显示培养基中VEGF-A和PDGF-AA水平升高。本研究表明UC-MSC分泌组促进胚胎发育和子宫内膜细胞功能，促进着床潜力。这些发现提示了它们在ART中支持着床前胚胎和改善母体子宫内膜容受性方面的潜在效用。

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来源期刊

Life sciences 医学-药学

CiteScore

12.20

自引率

1.60%

发文量

841

审稿时长

6 months

期刊介绍： Life Sciences is an international journal publishing articles that emphasize the molecular, cellular, and functional basis of therapy. The journal emphasizes the understanding of mechanism that is relevant to all aspects of human disease and translation to patients. All articles are rigorously reviewed. The Journal favors publication of full-length papers where modern scientific technologies are used to explain molecular, cellular and physiological mechanisms. Articles that merely report observations are rarely accepted. Recommendations from the Declaration of Helsinki or NIH guidelines for care and use of laboratory animals must be adhered to. Articles should be written at a level accessible to readers who are non-specialists in the topic of the article themselves, but who are interested in the research. The Journal welcomes reviews on topics of wide interest to investigators in the life sciences. We particularly encourage submission of brief, focused reviews containing high-quality artwork and require the use of mechanistic summary diagrams.