在进行与肝脏疾病治疗的相关研究中,肝细胞的体外培养是一个关键的问题。由于微环境的变化,肝细胞容易在体外培养中逐渐丧失正常表型和肝特异性功能。研究发现,在适当条件下,肝细胞可以形成多细胞球形聚集体,肝细胞在球形聚集体中呈现出与体内形态相仿的立体结构,细胞的表型和功能都得到了较好的维持。因此,如何调控肝细胞球形聚集体的形成以及尺寸形貌,得到具有高细胞密度、能在体外长时间保持高水平肝特异性功能的肝细胞球形聚集体是这方面研究的热点。本文对近年来肝细胞球形聚集体培养的研究成果进行了综述。首先介绍了肝细胞在体内的生长环境和肝脏的细胞结构,然后对培养肝细胞的生物材料各方面的性质,如材料的化学组成、表面电荷、亲疏水性质、表面形貌以及立体结构对肝细胞球形聚集体的影响进行了阐述;同时,也简要介绍了其他一些因素对肝细胞球形聚集体培养的影响;最后,对肝细胞球形聚集体培养的研究进展进行了总结和展望。
In the study of therapies for liver diseases, the in vitro culture of hepatocytes is one of the key issues since these cells are apt to lose their normal phenotype and liver-specific functions as a result of the change of culture microenvironment in vitro. It has been shown that the hepatoeyte spheroidal aggregates can better maintain the normal structures and functions of hepatocytes, and thereby are more attractive for therapeutic applications. In this article, the recent progress on hepatocyte spheroidal aggregates is reviewed. It starts with the introduction of the status of hepatocytes in sinusoids and cellular architecture of the liver, following with detail discussion on influences of biomaterials on the hepatoeyte spheroidal aggregates in terms of morphology and functions. These factors include chemical composition like galactose and RGD, charging property, hydrophilicity/ hydrophobicity, surface topology, and three-dimensional scaffolds. Other factors such as culture environment, addition of bioactive factors, and co-culture with other types of cells are also introduced briefly. Finally, perspectives of study on the spheroidal aggregates are suggested.