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培养的人结直肠癌匹配肿瘤和健康类器官的形态学改变。

Morphological alterations of cultured human colorectal matched tumour and healthy organoids.

作者信息

Kashfi Seyed Mohammad Hossein, Almozyan Sheema, Jinks Nicholas, Koo Bon-Kyoung, Nateri Abdolrahman S

机构信息

Cancer Genetics & Stem Cell Group, Cancer Biology, Division of Cancer and Stem Cells, School of Medicine, University of Nottingham, Nottingham, UK.

Wellcome Trust - Medical Research Council Stem Cell Institute, University of Cambridge, Cambridge, UK.

出版信息

Oncotarget. 2018 Jan 19;9(12):10572-10584. doi: 10.18632/oncotarget.24279. eCollection 2018 Feb 13.

Abstract

Organoids have extensive applications in many fields ranging from modelling human development and disease, personalised medicine, drug screening, etc. Moreover, in the last few years, several studies have evaluated the capacity of organoids as transplantation sources for therapeutic approaches and regenerative medicine. Nevertheless, depending on the origin of the cells and anatomical complications, an organoid transplant may make tissue regeneration difficult. However, some essential aspects of organoids including the morphological alterations and the growth pattern of the matched tumour and their healthy derived organoids have received less attention. Therefore, the current work focused on culturing matched healthy and tumour organoids from the same patient with colorectal cancer (CRC) and assessed their timed growth and structural differences on a daily basis. The healthy organoids underwent proliferation and branching morphogenesis, while the tumour organoids did not follow the same pattern, and the majority of them developed cystic structures instead. However, the number and size of tumour organoids were different from one patient to another. The differential morphological changes of the healthy versus human colonic tumour organoids likely linked to distinct molecular and cellular events during each day. Thus, while their specific structural features provide valuable models to study various aspects of human intestinal/colon tissue homeostasis and CRC which avoid or replace the use of animals in research, this model may also hold a great promise for the transplantation and regenerative medicine applications.

摘要

类器官在许多领域都有广泛应用,从模拟人类发育和疾病、个性化医疗、药物筛选等。此外,在过去几年中,多项研究评估了类器官作为治疗方法和再生医学移植来源的能力。然而,根据细胞来源和解剖学并发症,类器官移植可能会使组织再生变得困难。然而,类器官的一些重要方面,包括匹配肿瘤及其健康衍生类器官的形态改变和生长模式,受到的关注较少。因此,当前的工作重点是从同一位结直肠癌(CRC)患者培养匹配的健康和肿瘤类器官,并每天评估它们的定时生长和结构差异。健康类器官经历了增殖和分支形态发生,而肿瘤类器官则没有遵循相同的模式,大多数肿瘤类器官反而形成了囊性结构。然而,肿瘤类器官的数量和大小因患者而异。健康与人类结肠肿瘤类器官的不同形态变化可能与每天不同的分子和细胞事件有关。因此,虽然它们的特定结构特征为研究人类肠道/结肠组织稳态和CRC的各个方面提供了有价值的模型,避免或取代了研究中动物的使用,但这个模型在移植和再生医学应用方面也可能具有巨大的前景。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9fa7/5828197/d26eae951dd4/oncotarget-09-10572-g001.jpg

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