研究动态
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基质支架在子宫内膜源器官模型中的应用。

Matrix scaffolds for endometrium-derived organoid models.

发表日期:2023
作者: Silke De Vriendt, Celia Mesias Casares, Susana Rocha, Hugo Vankelecom
来源: Frontiers in Endocrinology

摘要:

子宮內膜對於哺乳動物的生殖至關重要,它接受並容納胚胎進行正確發育。儘管其關鍵作用,人們對內膜生物學(月經週期、胚胎互作)和疾病的機制了解不深。位於子宮內的隱藏位置以及缺乏合適的研究模型是造成這一知識差距的因素。最近,人們已經開發出從正常和疾病的內膜中提取的三維器官樣體模型。這些器官樣體緊密模擬了組織的上皮表型和(病理)生物學,包括體外再現月經週期。通常,器官樣體在由代理組織細胞外基質(ECM)製成的支架中生長,其中以小鼠腫瘤基底膜提取物最常用。然而,這些方法存在重要的限制,包括缺乏標準化和異種衍生,這很大程度上阻礙了臨床轉化。因此,研究者积極尋求更好的替代方案,包括全定義基質,以實現器官樣體的忠實和高效生長。本文我們總結了用於生長內膜衍生器官樣體的基質支架的最新發展,以及更先進的基於器官樣體的三維模型。我們討論了剩餘的不足和挑戰,以推動內膜器官樣體向定義和標準化的工具在基礎研究和轉化/臨床領域的應用。Copyright © 2023 De Vriendt, Casares, Rocha and Vankelecom.
The uterus-lining endometrium is essential to mammalian reproduction, receiving and accommodating the embryo for proper development. Despite its key role, mechanisms underlying endometrial biology (menstrual cycling, embryo interaction) and disease are not well understood. Its hidden location in the womb, and thereby-associated lack of suitable research models, contribute to this knowledge gap. Recently, 3D organoid models have been developed from both healthy and diseased endometrium. These organoids closely recapitulate the tissue's epithelium phenotype and (patho)biology, including in vitro reproduction of the menstrual cycle. Typically, organoids are grown in a scaffold made of surrogate tissue extracellular matrix (ECM), with mouse tumor basement membrane extracts being the most commonly used. However, important limitations apply including their lack of standardization and xeno-derivation which strongly hinder clinical translation. Therefore, researchers are actively seeking better alternatives including fully defined matrices for faithful and efficient growth of organoids. Here, we summarize the state-of-the-art regarding matrix scaffolds to grow endometrium-derived organoids as well as more advanced organoid-based 3D models. We discuss remaining shortcomings and challenges to advance endometrial organoids toward defined and standardized tools for applications in basic research and translational/clinical fields.Copyright © 2023 De Vriendt, Casares, Rocha and Vankelecom.