细胞间相互作用影响iPSc来源肝细胞的成熟

Cell Interaction Influences Maturation of Induced Pluripotent Stem Cell Derived Hepatocyte

获得功能性的肝细胞可用于研究肝细胞再生机理,并可为细胞移植和药物筛选提供生物材料。该研究采用四步法诱导多能干细胞分化成肝细胞,比较传代和不传代分化细胞的形态和肝细胞特异标志的差异表达。结果发现,利用诱导多能干细胞分化可获得白蛋白(albumin,ALB)阳性的成熟肝细胞,不传代法获得的细胞更接近于肝细胞形态,两组均获得甲胎蛋白(alphafetoprotein,AFP)和ALB阳性表达的细胞;GATA6(GATA binding protein 6)和HNF4A(hepatocyte nuclear factor 4 alpha)表达水平没有显著性差异,但不传代法分化细胞的AFP和ALB表达量高于传代法,存在显著性差异。结果提示,细胞因子与细胞间、多细胞间相互作用等因素影响多能干细胞的分化,细胞间相互作用有利于肝细胞定向诱导分化过程中肝细胞的成熟。

Study of pluripotent stem cell hepatocyte committed differentiation would be helpful to understand the mechanism of liver regeneration and obtain the biomaterials for regeneration medicine and drug screening. We established four stage inductions and compared the cell morphology and hallmarks of each differentiation stage between passage and no-passage. By committed differentiation, we derived ALB （albumin） positive mature hepatocyte from iPSc （induced pluripotent stem cell）. The phenotype of cells with no-passage was closer to mature hepatic cells. The two groups had AFP （alpha-fetoprotein） and ALB positive cells. There was no significant difference between the expression of GATA6 and HNF4A, but expression of AFP and ALB were significant higher in no-passage group than passage group. It concluded that pluripotent stem cell hepatocyte committed differentiation was one comprehensive process, which involving cytokine single, cell-to-cell and cell-tomatrix communication, keep the established cell interaction would benefit the hepatocyte mature.