新型二维/三维双体系癌症研究模型的建立
批准号:
32070796
项目类别:
面上项目
资助金额:
58.0 万元
负责人:
王霞
依托单位:
学科分类:
细胞外微环境与细胞间通讯
结题年份:
2024
批准年份:
2020
项目状态:
已结题
项目参与者:
王霞
中文摘要
癌症患者来源的原代肿瘤细胞二维(2D)培养技术长期以来存在效率低、存活差、难以长期稳定培养等一系列问题,是目前亟待解决的技术瓶颈。三维(3D)肿瘤类器官作为新型癌症研究模型具有独特的优势和巨大的潜力,但体外扩增速率较慢等问题尚待解决。本项目迎合问题导向和临床需求导向,目标是建立一个高效、长期、稳定、快速增殖和广谱性的结直肠癌患者来源的2D肿瘤细胞培养技术和3D气液界面肿瘤类器官培养技术,并保留其来源肿瘤组织的生物学特征和异质性特征。该技术体系的特色是充分结合并发挥2D和3D培养体系各自的优势,灵活选择运用,解决单独使用2D培养体系或3D培养体系时各自的局限性,开创一个新型的2D/3D双体系癌症研究模型,将解决癌症研究模型领域诸多尚未解决的技术瓶颈问题,实现技术和思路上的突破和创新。该技术平台将推动癌症的个性化治疗和精准治疗的探索和发展,促进基础研究成果向临床应用的转化。
英文摘要
Currently, it is still a great challenge for the stability, long-term culture and maintenance of 2D cancer cells derived from patients, due to the inefficient culture method available so far. 3D cancer organoids have emerged as powerful preclinical tumor model systems with unique advantages, as well as limitations to be improved. To address the challenges and limitations of current cancer models, and to meet clinical needs, it is necessary to develop a new cancer model. The objective of this research work is to establish a colorectal cancer patient-derived 2D cancer cell culture system and 3D air-liquid interface (ALI) cancer organoids culture system, which potentially present properties of highly efficiency, long-term, stability, robust proliferation and broad-spectrum. These cultured 2D cancer cells and ALI organoids faithfully recapitulate the histopathologic and molecular characteristics of the primary tumors. By effectively optimizing and flexibly utilizing the respective advantages of 2D and 3D cultural systems, the 2D&3D union culture system will definitely be a very powerful platform to address the limitations of using 2D culture system or 3D culture system alone. This novel 2D&3D union culture system will achieve breakthroughs and innovations in technology and theory. It will promote the exploration and development of personalized cancer treatment, and promote the transformation of basic research into clinical applications.
传统的二维肿瘤细胞系虽然简便易行,但建立新的细胞系却是一项耗时且效率极低的任务。更为重要的是,它无法真实再现原发性肿瘤的多样性,因此难以满足个性化精准医疗的需求。然而,肿瘤类器官技术则能在体外高度还原体内肿瘤的原始特征,为药物研发、患者治疗反应的预测以及个性化医疗方案的制定提供了广阔的应用前景。本项目成功构建了高效稳定的结直肠癌二维肿瘤细胞系与三维气液界面肿瘤类器官培养体系。这一创新的二维和三维联合培养系统(2D&3D 模型)不仅精准地再现了原发性肿瘤的特征,更捕捉到了肿瘤间和肿瘤内药物反应及致瘤性的异质性。这一研究成果已在2022年的《Advanced Science》杂志上发表,引起了学界的广泛关注。在此基础上,本项目进一步突破了技术壁垒,成功建立了结直肠癌原发肿瘤组织中单个肿瘤细胞来源的肿瘤细胞系。深入鉴定并表征了原发肿瘤组织里的转移种子细胞,揭示了转移的起源和机制,这一重要成果于2024年3月19日在线刊登于《Journal of Experimental Medicine》 (JEM)杂志上,其标题为Distinct molecular profiles drive multifaceted characteristics of colorectal cancer metastatic seeds。
新型二维/三维双体系癌症研究模型的建立
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批准号:--
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项目类别:--
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资助金额:58万元
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批准年份:2020
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负责人:王霞
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依托单位:
国内基金
海外基金