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Three-dimensional bio-printing of primary human hepatocellular carcinoma for personalized medicine
Biomaterials ( IF 14.0 ) Pub Date : 2020-09-22 , DOI: 10.1016/j.biomaterials.2020.120416
Feihu Xie , Lejia Sun , Yuan Pang , Gang Xu , Bao Jin , Haifeng Xu , Xin Lu , Yiyao Xu , Shunda Du , Yanan Wang , Shi Feng , Xinting Sang , Shouxian Zhong , Xin Wang , Wei Sun , Haitao Zhao , Hongbing Zhang , Huayu Yang , Pengyu Huang , Yilei Mao

Hepatocellular carcinoma (HCC) is one of the most lethal tumors worldwide. This study aims to address the lack of faithful and available in vitro models for patient-specific drug screening for HCC. We recently established a novel modeling system using three-dimensional (3D) bioprinting technology and constructed hepatorganoids with HepaRG cells, which retain the liver function and prolong the survival of mice with liver failure after abdominal transplantation. Here we extend this modeling system to establish individualized model for hepatocellular carcinoma. HCC specimens were obtained from six patients after surgery. Primary HCC cells were isolated and mixed with gelatin and sodium alginate to form the bioink for printing. Patient-derived three-dimensional bio-printed HCC (3DP-HCC) models were successfully established afterward and grew well during long-term culture. These models retained the features of parental HCCs, including stable expression of the biomarker, stable maintenances of the genetic alterations and expression profiles. 3DP-HCC models are capable of displaying the results of drug screening intuitively and quantitatively. In conclusion, 3DP-HCC models are faithful in vitro models that are reliable in long-term culture and able to predict patient-specific drugs for personalized treatment.



中文翻译:

原发性人类肝细胞癌的三维生物打印作为个性化药物

肝细胞癌(HCC)是全球最致命的肿瘤之一。这项研究的目的是解决针对HCC的患者特异性药物筛查缺乏可靠和可用的体外模型的问题。我们最近建立了一个使用三维(3D)生物打印技术的新型建模系统,并用HepaRG细胞构建了类肝生物素,该类肝素保留了肝功能并延长了腹部移植后肝衰竭小鼠的生存期。在这里,我们扩展此建模系统以建立肝细胞癌的个性化模型。手术后从六名患者获得肝癌标本。分离原代HCC细胞,并与明胶和海藻酸钠混合以形成用于印刷的生物墨水。随后成功建立了患者来源的三维生物打印HCC(3DP-HCC)模型,并且在长期培养过程中生长良好。这些模型保留了亲本肝癌的特征,包括生物标志物的稳定表达,遗传改变和表达谱的稳定维持。3DP-HCC模型能够直观,定量地显示药物筛选的结果。总之,3DP-HCC模型是可靠的体外模型,在长期培养中是可靠的,并且能够预测针对患者的个性化治疗药物。3DP-HCC模型能够直观,定量地显示药物筛选的结果。总之,3DP-HCC模型是可靠的体外模型,在长期培养中是可靠的,并且能够预测针对患者的个性化治疗药物。3DP-HCC模型能够直观,定量地显示药物筛选的结果。总之,3DP-HCC模型是可靠的体外模型,在长期培养中是可靠的,并且能够预测针对患者的个性化治疗药物。

更新日期:2020-09-29
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