中文摘要
肿瘤微环境对肝癌的恶性表型具有重要作用。现有的体外肝癌模型对体内三维微环境的仿真性不足,导致研究结果的体内复制性差,极大降低了研究效率。因此,建立一套仿真度更高的体外肝癌模型,对于优化肝癌基础及临床研究具有重要意义。项目组前期研究及文献均证实,肝脏脱细胞支架具有天然的细胞外基质成分、三维多孔结构和微血管网络,生物相容性良好,是体外重建肝脏组织的理想材料。我们设想利用肝脏脱细胞支架能够构建高度仿真的肝癌三维动态培养模型,并以此为平台建立个体化的抗癌药物敏感谱。为此,本项目拟:(1)研究确定关键技术参数,构建基于肝脏脱细胞支架的肝癌三维动态培养模型;(2)通过对肝癌发生发展、侵袭转移、耐药性等生物学行为进行研究,评价模型的可行性和优势;(3)利用成功构建的肝癌三维动态模型培养患者原代肝癌细胞,结合药敏试验建立个体化的抗癌药物敏感谱,为实现肝癌的个体化治疗奠定实验基础。
英文摘要
Interaction between the hepatoma cells and microenvironment plays an important role in malignant phenotype of the liver cancer. However, the existing in vitro liver cancer models are unable to simulate the 3D microenvironment in vivo, resulting in poor intracorporal replication of research findings especially the sensitivity of anti-cancer drugs, and significantly reducing the research efficiency. Therefore, to establish a more emulational 3D liver cancer model in vitro is very important for basic and clinical research of liver cancer. Our previous research and other literature has demonstrated that decellularized liver scaffolds, which provide natural extracellular matrix component, three-dimensional porous structure and microvascular network for liver tissue reconstruction in vitro, could be the ideal material for liver tissue engineering. This project intends to establish a 3D dynamic liver cancer model on the basis of decellularized liver scaffold. This model will potentially provide a more emulational research platform for development, invasion, metastasis, and drug resistance of liver cancer. This model will then be used for cultivation of patients’ primary liver cancer cells, and establishing an individualized drug sensitive spectrum through anti-cancer drug sensitive test. This project chould provide experiment basis for the individualized treatment of liver cancer.
