子宫源性脱细胞细胞外基质介导的子宫内膜再生和生育能力增强,Advanced Functional Materials

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子宫源性脱细胞细胞外基质介导的子宫内膜再生和生育能力增强
Advanced Functional Materials ( IF 18.5 ) Pub Date : 2023-05-17 , DOI: 10.1002/adfm.202214291
Jungho Ahn ₁ , Tugce Sen ₂ , Danbi Lee ₃ , Hyeonji Kim ₂ , Jae Yeon Lee ₄ , Hwa Seon Koo ₅ , Jae Yun Kim ₆ , Jisoo Kim ₆ , Jinah Jang _{2,

6,

7} , Youn‐Jung Kang ₁ , Dong‐Woo Cho ₂

Affiliation

组织特异性脱细胞细胞外基质概括了天然 ECM 的复杂性，根据其内在特征创建了器官特异性微环境。在这里，开发了含有来自子宫内膜特异性层或整个子宫的子宫衍生的脱细胞细胞外基质（UdECM）的水凝胶。UdECM 作为有效的器官特异性生物材料，表明宫内 UdECM 给药可诱导子宫内膜再生和生育力增强。此外，UdECM 给药改变了自然杀伤细胞亚群的概况，使其表现出更成熟和细胞毒性更低的特征，为成功着床和蜕膜化提供了有利的子宫环境。有趣的是，胰岛素样生长因子 1 和胰岛素样生长因子结合蛋白 3 作为有助于 UdECM 介导的子宫内膜再生的关键调节因子被发现。此外，人类子宫组织的离体培养表明，不同来源的UdECM根据患者的子宫内膜状况表现出不同的治疗效果，表明它们可以作为一种治疗干预措施，为子宫环境较差的不孕患者提供个性化的再生医学。

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Uterus-Derived Decellularized Extracellular Matrix-Mediated Endometrial Regeneration and Fertility Enhancement

Tissue-specific decellularized extracellular matrix recapitulates the complexity of natural ECMs, creating an organ-specific microenvironment based on its intrinsic characteristics. Here, hydrogels containing uterus-derived decellularized extracellular matrix (UdECMs) from the endometrium-specific layer or the entire uterus are developed. UdECMs serve as effective organ-specific biomaterials, displaying that intrauterine UdECM administration induces endometrial regeneration and fertility enhancement. Moreover, UdECM administration alters the profile of natural killer cell subpopulations to exhibit more mature and less cytotoxic features, providing a favorable uterine environment for successful implantation and decidualization. Interestingly, insulin-like growth factor 1 and insulin-like growth factor-binding protein 3 as key regulatory factors that contribute to UdECM-mediated endometrial regeneration are discovered. Furthermore, ex vivo culture of human uterine tissues reveals that UdECMs of different origins exhibit distinct therapeutic effects based on the endometrial conditions of patients, suggesting their uses as a therapeutic intervention providing personalized regenerative medicine for infertile patients with a poor uterine environment.

更新日期：2023-05-17

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