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胃类器官——用于研究胃发育和迈向个体化医疗之路的体外模型系统。

Gastric organoids-an in vitro model system for the study of gastric development and road to personalized medicine.

机构信息

Department of Visceral, Thoracic and Vascular Surgery, Medical Faculty and University Hospital Carl Gustav Carus, Technische Universität Dresden, Dresden, Germany.

Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna Biocenter (VBC), Vienna, Austria.

出版信息

Cell Death Differ. 2021 Jan;28(1):68-83. doi: 10.1038/s41418-020-00662-2. Epub 2020 Nov 22.

Abstract

Gastric cancer ranks as the fifth most common human malignancy and the third leading cause of cancer related deaths. Depending on tumor stage, endoscopic or surgical resection supported by perioperative chemotherapy is the only curative option for patients. Due to late clinical manifestation and missing reliable biomarkers, early detection is challenging and overall survival remains poor. Organoids are cell aggregates cultured in three-dimensions that grow with similar characteristics as their tissue-of-origin. Due to their self-renewal and proliferative capacity, organoids can be maintained long term in culture and expanded in many cases in an unlimited fashion. Patient-derived organoid (PDO) libraries function as living biobanks, allowing the in depth analysis of tissue specific function, development and disease. The recent successful establishment of gastric cancer PDOs opens up new perspectives for multiple translational clinical applications. Here, we review different adult stem cell derived gastric organoid model systems and focus on their establishment, phenotypic and genotypic characterizations as well as their use in predicting therapy response.

摘要

胃癌是第五大常见人类恶性肿瘤,也是癌症相关死亡的第三大主要原因。根据肿瘤分期,内镜或手术切除联合围手术期化疗是患者唯一的治愈选择。由于临床表现较晚且缺乏可靠的生物标志物,早期检测具有挑战性,总体生存率仍然较差。类器官是在三维环境中培养的细胞聚集体,其生长特性与其组织来源相似。由于具有自我更新和增殖能力,类器官可以在培养中长期维持,并在许多情况下以无限的方式扩增。患者来源的类器官(PDO)文库作为活体生物库,可深入分析组织特异性功能、发育和疾病。最近成功建立的胃癌 PDO 为多种转化临床应用开辟了新的前景。在这里,我们综述了不同的成人干细胞衍生的胃类器官模型系统,并重点介绍了它们的建立、表型和基因型特征以及在预测治疗反应中的应用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/2d47/7852679/885022856629/41418_2020_662_Fig1_HTML.jpg

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