Extracellular Vesicles Derived From Endometrial Stem Cells Preconditioned With PGE2-Reverse Myofibroblast Phenotype in Mare Endometrial Cells: A Novel Anti-Fibrotic Approach

IF 3 3区 生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY
Lidice Méndez-Pérez, Belén O. Ibáñez, Sebastián Rodríguez, Yat Sen Wong, Diego Caamaño, Felipe I. Navarrete, Joel Cabezas, Ana C. Mançanares, Carlos Escudero, Lleretny Rodríguez-Álvarez, Fidel Ovidio Castro
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引用次数: 0

Abstract

Endometrial fibrosis in mares compromises fertility through aberrant extracellular matrix deposition and sustained myofibroblast activation. Conventional interventions fail to reverse these pathological alterations, necessitating innovative, mechanism-focused therapies. In this study, we pioneered the use of prostaglandin E2 (PGE2) preconditioning of equine endometrial-derived mesenchymal stem cells (ET-eMSCs) and their extracellular vesicles (EVs) to target fibrotic processes directly. ET-eMSCs were isolated from mare endometrial biopsies pretreated with PGE2 to enhance their anti-fibrotic secretome, and EVs were subsequently harvested. In vitro assays demonstrated that PGE2-preconditioned ET-eMSCs and their EVs inhibited α-smooth muscle actin expression, reduced collagen I deposition, and restored key endometrial markers of receptivity and proliferation. These findings establish the first evidence that PGE2-enhanced ET-eMSC-derived EVs can exert anti-fibrotic effects in an in vitro model of equine endometrial fibrosis. This study provides a robust translational framework for developing targeted regenerative therapies for fibrotic diseases across species, with potential applications in human reproductive medicine.

子宫内膜干细胞经pge2逆转肌成纤维细胞表型预处理后的细胞外囊泡:一种新的抗纤维化方法
母马子宫内膜纤维化通过异常的细胞外基质沉积和持续的肌成纤维细胞激活而损害生育能力。传统的干预措施无法逆转这些病理改变,因此需要创新的、以机制为重点的治疗方法。在这项研究中,我们率先使用前列腺素E2 (PGE2)预处理马子宫内膜源性间充质干细胞(ET-eMSCs)及其细胞外囊泡(ev)直接靶向纤维化过程。从母子宫内膜活检组织中分离出ET-eMSCs,经PGE2预处理以增强其抗纤维化分泌组,随后收获ev。体外实验表明,pge2预处理的ET-eMSCs及其ev抑制α-平滑肌肌动蛋白表达,减少I型胶原沉积,恢复子宫内膜容受性和增殖的关键标志物。这些发现首次证明了pge2增强的et - emsc衍生的ev可以在马子宫内膜纤维化的体外模型中发挥抗纤维化作用。该研究为开发跨物种纤维化疾病的靶向再生疗法提供了一个强大的翻译框架,在人类生殖医学中具有潜在的应用前景。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
5.20
自引率
0.00%
发文量
78
审稿时长
6-12 weeks
期刊介绍: Molecular Reproduction and Development takes an integrated, systems-biology approach to understand the dynamic continuum of cellular, reproductive, and developmental processes. This journal fosters dialogue among diverse disciplines through primary research communications and educational forums, with the philosophy that fundamental findings within the life sciences result from a convergence of disciplines. Increasingly, readers of the Journal need to be informed of diverse, yet integrated, topics impinging on their areas of interest. This requires an expansion in thinking towards non-traditional, interdisciplinary experimental design and data analysis.
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