Despite having yielded extensive breakthroughs in cancer research, traditional 2D cell cultures have limitations in studying cancer progression and metastasis and screening therapeutic candidates. 3D systems can allow cells to grow, migrate, and interact with each other and the surrounding matrix, resulting in more realistic constructs. Furthermore, interactions between host tissue and developing tumors influence the susceptibility of tumors to drug treatments. Host-liver colorectal-tumor spheroids composed of primary human hepatocytes, mesenchymal stem cells (MSC) and colon carcinoma HCT116 cells were created in simulated microgravity rotating wall vessel (RWV) bioreactors. The cells were seeded on hyaluronic acid-based microcarriers, loaded with liver-specific growth factors and ECM components. Only in the presence of MSC, large tumor foci rapidly formed inside the spheroids and increased in size steadily over time, while not greatly impacting albumin secretion from hepatocytes. The presence of MSC appeared to drive self-organization and formation of a stroma-like tissue surrounding the tumor foci and hepatocytes. Exposure to a commonly used chemotherapeutic 5-FU showed a dose-dependent cytotoxicity. However, if tumor organoids were allowed to mature in the RWV, they were less sensitive to the drug treatment. These data demonstrate the potential utility of liver tumor organoids for cancer progression and drug response modeling.

中文翻译：

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间充质干细胞支持宿主-肝脏结直肠肿瘤类器官的生长和组织，并可能对化学疗法产生抗性。

尽管在癌症研究中取得了重大突破，但传统的2D细胞培养在研究癌症进展和转移以及筛选治疗候选药物方面仍存在局限性。3D系统可以使细胞与周围的基质相互生长，迁移和相互作用，从而产生更逼真的构造。此外，宿主组织与发展中的肿瘤之间的相互作用影响肿瘤对药物治疗的敏感性。在模拟微重力旋转壁血管（RWV）生物反应器中创建了由原代人肝细胞，间充质干细胞（MSC）和结肠癌HCT116细胞组成的宿主-肝脏结直肠肿瘤球体。将细胞接种在基于透明质酸的微载体上，该微载体上装有肝脏特异性生长因子和ECM成分。只有在MSC存在的情况下，大的肿瘤病灶在球体内迅速形成，并且随着时间的推移大小不断增加，而不会极大地影响肝细胞白蛋白的分泌。MSC的存在似乎促进了肿瘤灶和肝细胞周围的基质样组织的自组织和形成。暴露于常用的化学疗法5-FU显示剂量依赖性细胞毒性。但是，如果让肿瘤类器官在RWV中成熟，它们对药物治疗的敏感性就会降低。这些数据证明了肝肿瘤类器官对于癌症进展和药物反应模型的潜在实用性。MSC的存在似乎驱动了自组织和围绕肿瘤灶和肝细胞的基质样组织的形成。暴露于常用的化学疗法5-FU显示剂量依赖性细胞毒性。但是，如果让肿瘤类器官在RWV中成熟，它们对药物治疗的敏感性就会降低。这些数据证明了肝肿瘤类器官对于癌症进展和药物反应模型的潜在实用性。MSC的存在似乎驱动了自组织和围绕肿瘤灶和肝细胞的基质样组织的形成。暴露于常用的化学疗法5-FU显示剂量依赖性细胞毒性。但是，如果让肿瘤类器官在RWV中成熟，它们对药物治疗的敏感性就会降低。这些数据证明了肝肿瘤类器官对于癌症进展和药物反应模型的潜在实用性。