摘要
传统的肿瘤培养模型包括二维肿瘤细胞培养和异种移植物模型,前者存在缺乏肿瘤异质性、模型失真等问题,后者存在建模成功率偏低、耗时长、价格贵等缺点。近年出现的体外三维(3D)培养模型可以较好地模拟体内肿瘤的空间结构与生长环境,保留肿瘤细胞的病理与遗传学特征,并反映肿瘤细胞间、肿瘤与微环境间的复杂相互作用,逐渐成为肿瘤机制研究、药物筛选和肿瘤个体化治疗的有力工具。球状体、类器官、微流控装置等3D肿瘤模型技术日渐成熟,共培养、3D生物打印、气液界面等新技术的应用使模型的仿真性进一步提高,一些模型可重建肿瘤微环境,一些模型甚至具有内源性免疫成分与微脉管系统。近年来,有学者将异种移植物模型与类器官技术相结合,构建了体内/体外配对的生物模型库,发挥出两种技术的优势,并可针对具有特定分子学特征的肿瘤进行个体化精准疗法研发。至今,上述技术已广泛应用于结直肠癌研究领域。作者团队目前研究采用结直肠癌患者来源的3D微肿瘤模型指导术后化疗药物选择,建模成功率高、药物筛选实验结果理想。相信随着相关技术的进步,3D肿瘤模型将在结直肠癌研究、药物研发与转化、疗法筛选及个体化治疗等领域发挥巨大作用。
Conventional tumor culture models include two-dimensional tumor cell cultures and xenograft models.The former has disadvantages including lack of tumor heterogeneity and poor clinical relevance,while the latter are limited by the slow growth,low engraftment successful rate,and high cost.In recent years,in vitro three-dimensional(3D)tumor models have emerged as the tool to better recapitulate the spatial structure and the in vivo environment of tumors.In addition,they preserve the pathological and genetic features of tumor cells and reflect the complex intracellular and extracellular interactions of tumors,which have become a powerful tool for investigating the tumor mechanism,drug screening,and personalized cancer treatment.3D tumor model technologies such as spheroids,organoids,and microfluidic devices are maturing.Application of new technologies such as co-culture,3D bioprinting,and air-liquid interface has further improved the clinical relevance of the models.Some models recapitulate the tumor microenvironment,and some can even reconstitute endogenous immune components and microvasculature.In recent years,some scholars have combined xenograft models with organoid technology to develop matched in vivo/in vitro model biobanks,giving full play to the advantages of the two technologies,and providing an ideal research platform for individualized precision therapy for specific molecular targets in certain subtypes of tumors.So far,the above technologies have been widely applied in the field of colorectal cancer research.Our research team is currently studying upon the application of patient-derived tumor cell-like clusters,a self-assembly 3D tumor model,in guiding the selection of postoperative chemotherapy regimens for colorectal cancer.A high modeling success rate and satisfactory results in the drug screening experiments have been achieved.There is no doubt that with the advancement of related technologies,3D tumor models will play an increasingly important role in the research and clinical practice of colorectal
作者
王晨童
周皎琳
林国乐
尹申意
丛林
张冠南
安杨
邱小原
Wang Chentong;Zhou Jiaolin;Lin Guole;Yin Shenyi;Cong Lin;Zhang Guannan;An Yang;Qiu Xiaoyuan(Department of General Surgery,Peking Union Medical College Hospital,Peking Union Medical College,Chinese Academy of Medical Sciences,Beijing 100730,China;State Key Laboratory of Natural and Biomimetic Drugs,Institute of Molecular Medicine,Department of Biomedical Engineering,College of Engineering,Peking University,Beijing 100080,China)
出处
《中华肿瘤杂志》
CAS
CSCD
北大核心
2023年第6期464-470,共7页
Chinese Journal of Oncology
