瑞士联邦理工学院Matthias P. Lutolf、L. Francisco Lorenzo-Martín研究组在研究中取得进展。他们发现患者衍生的微型结肠能长期模拟肿瘤微环境的复杂性。2024年7月2日，国际学术期刊《自然-生物技术》发表了这一成果。

为了克服类器官的局限性，研究人员采用组织工程和微制造技术制备了具有拓扑生物学复杂性、患者特异性的癌症类器官。研究人员着眼于结直肠癌，生成了由长寿命肠形人类结肠上皮（"迷你结肠"）组成的微型组织，这些组织将癌细胞及其原生肿瘤微环境稳定地整合在一起，经过优化可对细胞动态进行实时、高分辨率评估。

研究通过以下几种应用展示了这一系统的潜力：全面评估抗癌疗法的药效、毒性和耐药性；发现由癌症相关成纤维细胞引发癌症侵袭的机制；以及识别肿瘤微环境不同成分之间的免疫调节作用。类似的方法适用于不同类型的肿瘤。

据了解，现有的类器官模型由于缺乏充足的细胞多样性、组织层次结构、生物持久性和实验灵活性而无法完全再现癌症的复杂性。因此，许多多因素诱导的癌症，尤其与肿瘤微环境有关的过程很难在体外进行研究。

附：英文原文

Title: Patient-derived mini-colons enable long-term modeling of tumor–microenvironment complexity

Author: Lorenzo-Martn, L. Francisco, Broguiere, Nicolas, Langer, Jakob, Tillard, Lucie, Nikolaev, Mikhail, Coukos, George, Homicsko, Krisztian, Lutolf, Matthias P.

Issue&Volume: 2024-07-02

Abstract: Existing organoid models fall short of fully capturing the complexity of cancer because they lack sufficient multicellular diversity, tissue-level organization, biological durability and experimental flexibility. Thus, many multifactorial cancer processes, especially those involving the tumor microenvironment, are difficult to study ex vivo. To overcome these limitations, we herein implemented tissue-engineering and microfabrication technologies to develop topobiologically complex, patient-specific cancer avatars. Focusing on colorectal cancer, we generated miniature tissues consisting of long-lived gut-shaped human colon epithelia (‘mini-colons’) that stably integrate cancer cells and their native tumor microenvironment in a format optimized for real-time, high-resolution evaluation of cellular dynamics. We demonstrate the potential of this system through several applications: a comprehensive evaluation of drug effectivity, toxicity and resistance in anticancer therapies; the discovery of a mechanism triggered by cancer-associated fibroblasts that drives cancer invasion; and the identification of immunomodulatory interactions among different components of the tumor microenvironment. Similar approaches should be feasible for diverse tumor types.

DOI: 10.1038/s41587-024-02301-4

Source: https://www.nature.com/articles/s41587-024-02301-4