| 摘要: | 子宮內膜由上皮細胞與基質細胞所構成，在女性生殖系統中扮演關鍵角色，受到賀爾蒙調控，參與月經週期、胚胎著床、妊娠及分娩等重要生理過程。其功能的正常與否不僅影響生育能力，也與女性整體健康密切相關。而子宮內膜異位症是一種慢性、炎症性且雌激素依賴性的疾病，其特徵為類似子宮內膜的組織出現在子宮腔外，引發疼痛、不孕及其他併發症。儘管其致病機制尚未完全明確，但目前認為與荷爾蒙調控密切相關，因此臨床上常採用賀爾蒙療法進行治療。由於動物模型存在物種間生理差異，限制了研究結果的可比較性，因此發展具生理重現性的體外模型成為一項重要且迫切的課題。本研究分為三部分。第一部分運用三維生物列印技術，以第一型膠原蛋白作為生物墨水，同時培養人類子宮內膜上皮細胞與基質細胞，建構具有立體結構且包含細胞間交互作用的複合型模型，以模擬天然子宮內膜組織的微環境與結構特性，並優化列印條件以提升模型穩定性與重現性。第二部分則透過荷爾蒙刺激，分別使用雌激素與黃體激素，模擬生理性與病理性的賀爾蒙環境，進一步觀察細胞在不同條件下的行為變化，包括細胞遷移、增生、侵襲等。第三部分則依據Sampson’s theory作為參考理論，於同一培養皿中額外設置一個無細胞膠體作為對照，用以釐清細胞的遷移途徑，藉由觀察細胞是否因荷爾蒙刺激而飄落並附著於該無細胞膠體，同時評估細胞在異位位置的存活情形。期望藉此模型更真實地重現子宮內膜異位症的病理發展過程，並釐清荷爾蒙在異位生長與病灶形成中的角色，為未來疾病機轉研究與治療策略提供新方向。;The endometrium, composed of epithelial and stromal cells, plays a crucial role in the female reproductive system. Under hormonal regulation, it participates in essential physiological processes such as the menstrual cycle, embryo implantation, pregnancy, and childbirth. The proper functioning of the endometrium not only influences fertility but is also closely linked to women′s overall health. Endometriosis is a chronic, inflammatory, and estrogen-dependent disease characterized by the presence of endometrium-like tissue outside the uterine cavity, often resulting in pain, infertility, and other complications. Although the exact pathogenesis remains unclear, it is believed to be closely associated with hormonal regulation, and hormone therapy is commonly applied in clinical practice. However, physiological differences across species limit the comparability of results from animal models, making the development of physiologically relevant in-vitro models an urgent need. In this study, we established a three-part experimental design. First, a composite 3D model was constructed using three-dimensional bioprinting technology, with type I collagen as the bio-ink. Human endometrial epithelial and stromal cells were co-cultured to recreate the microenvironment and structural features of native endometrial tissue, enabling cell and cell interactions within a three-dimensional framework. Printing parameters were optimized to improve stability and reproducibility. Second, hormonal stimulation with estrogen and progesterone was applied to simulate both physiological and pathological conditions, enabling investigation of cellular behaviors such as migration, proliferation, and invasion under different hormonal environments. Third, following Sampson’s theory, an additional cell-free construct was introduced into the same culture dish as a control to clarify the potential migration pathways. By observing whether cells detached and reattached to the cell-free construct and survived at ectopic sites. This model aims to better replicate the pathological development of survived at ectopic sites. This model aims to better replicate the pathological development of endometriosis and clarify the role of hormones in ectopic growth and lesion formation, offering a new direction for future mechanistic studies and therapeutic strategies. |
