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    Please use this identifier to cite or link to this item: http://ir.lib.ncu.edu.tw/handle/987654321/94803


    Title: 開發體外培養子宮內膜類組織應用於子宮沾黏症候群相關研究;Development of In-vitro Artificial Endometrial Tissues for Applications in Intrauterine Adhesions
    Authors: 楊勳岳;Yang, Syun-Yue
    Contributors: 生物醫學工程研究所
    Keywords: 子宮沾黏症候群;三維培養;子宮內膜類器官;3D列印;生物支架;Intrauterine adhesions;3D culture;Endometrial organoid;3D printing;Bioscaffold
    Date: 2024-07-29
    Issue Date: 2024-10-09 15:30:59 (UTC+8)
    Publisher: 國立中央大學
    Abstract: 子宮內膜對女性的生殖健康至關重要,由幾種不同類型的上皮細胞和基質細胞組成,上皮細胞與基質細胞之間的細胞通訊對於子宮內膜的正常功能至關重要。子宮沾黏症候群(Intrauterine Adhesions,IUA)主要發生在刮宮術(Dilation and Curettage,D&C)後,也可能在子宮動脈栓塞手術後發生。這主要是由於子宮內膜受損,導致基質細胞異常增生,使內膜之間產生組織沾黏。過去,治療子宮沾黏通常使用子宮鏡和宮內節育器以及激素刺激來治療;近年來,研究發現使用水凝膠作為術後預防以及細胞治療的方式具有潛力。本研究著重於水凝膠治療效果和子宮內膜類組織的開發。隨著類器官培養技術的快速發展,許多體外模擬的類器官可以呈現體內器官的部分功能。在第一部分,本研究開發了一種方法,通過結合人類子宮內膜上皮細胞(human endometrial epithelial cells,hEEC)和人類子宮內膜基質細胞(human endometrial stromal cells,hESC)以及3D 列印技術,利用體外培養技術培育子宮內膜類組織。此研究以膠原蛋白作為支架,基質細胞預先與膠原蛋白墨水(Collgel®)混合,然後通過3D 列印出圓盤,將上皮細胞種植在支架表面,形成人工子宮內膜類組織(artificial Endometrial Tissues,AEC)。後續對AEC進行染色及觀察細胞在支架內的生長形態,旨在建立體外子宮模型,未來可用於觀察子宮沾黏的體外模型以及藥篩平台的測試。第二部分則進行動物實驗。實驗將小鼠的子宮通過針頭刺傷模擬子宮受損,然後注射水凝膠,觀察術後預防的效果。這一階段旨在比較動物模型與體外模型之間的差異,並評估水凝膠的治療效果。;The endometrium is crucial for women′s reproductive health, consisting of different types of epithelial and stromal cells. Communication between epithelial and stromal cells is essential for the physiological functions of the endometrium. Intrauterine adhesions (IUA) commonly occur after dilation and curettage (D&C) procedures and can also follow uterine artery embolization. This condition arises from endometrial damage leading to abnormal proliferation of stromal cells, resulting in tissue adhesions between the endometrial layers. Historically, IUA treatments have involved hysteroscopy, intrauterine devices, and hormone therapy. Recently, research has explored the use of hydrogels for postoperative prevention and cell therapy for treatment.This study focuses on the effectiveness of hydrogel treatment and the development of endometrial-like tissues. With the rapid advancement of organoid culture techniques, many in vitro organoids can mimic some functions of in vivo organs. In the first part of this study, we developed a method combining human endometrial epithelial cells (hEEC) and human endometrial stromal cells (hESC) with 3D printing technology to cultivate endometrial-like tissues in vitro. Collagen was used as a scaffold, with stromal cells pre-mixed with collagen ink (Collgel®) and 3D printed into discs. Epithelial cells were then seeded on the scaffold surface to form artificial endometrial tissues (AEC). These AECs were subsequently stained and observed to examine cell growth patterns within the scaffold. This phase aims to establish an in vitro uterine model, which can later be used to observe IUA models and test drug screening platforms.The second part of the study involves animal experiments. The uteri of mice were damaged using needles to simulate endometrial injury, followed by hydrogel injection to observe the effectiveness of postoperative prevention. This phase aims to compare differences between animal models and in vitro models and to evaluate the therapeutic effects of the hydrogel.
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