Mixed-ligand modification of polyamidoamine dendrimers to develop an effective scaffold for maintenance of hepatocyte spheroids.
Mixed-ligand modification of polyamidoamine dendrimers to develop an effective scaffold for maintenance of hepatocyte spheroids.
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聚酰胺胺树枝状聚合物的混合配体修饰，开发用于维持肝细胞球体的有效支架。
DOI：
10.1002/jbm.a.10419
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发表时间：
2003
期刊：
影响因子：
--
通讯作者：
K. Yagi
中科院分区：
文献类型：
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作者：
S. Higashiyama;M. Noda;M. Kawase;K. Yagi
与单层培养相比，已知肝细胞球状体可长期维持肝功能。我们发现，肝细胞形成球状体时，培养的聚酰胺-胺树枝状聚合物修饰的果糖。由于半乳糖是肝细胞质膜上脱唾液酸糖蛋白受体的配体，因此选择其作为另一种修饰配体，以维持球状体的长期粘附。同时修饰的树枝状大分子与果糖和半乳糖有显着的效果的时间长度的球体粘附。在用果糖和半乳糖修饰的树枝状聚合物（F/G树枝状聚合物）上培养的肝细胞球体中观察到细胞凋亡和坏死的抑制。此外，肝细胞球体上培养的F/G树枝状聚合物有更高的活性的肝脏特异性功能，如尿素合成和白蛋白基因表达，比那些培养的单配体修饰的树枝状聚合物。检测热休克蛋白（HSP）基因的表达，以评估细胞对支架的应激反应。在F/G树枝状聚合物上培养的肝细胞具有非常低的HSP 60和HSP 70 mRNA表达水平。因此，固定化的混合配体修饰的树枝状聚合物可以产生一个合适的表面肝细胞球体的形成。这些树枝状聚合物可能是一个强大的工具，通过选择适合每种细胞类型的配体，为肝细胞以外的细胞生成定制的支架。
Compared with a monolayer culture, hepatocyte spheroids are known to maintain liver function for long periods. We found that hepatocytes formed spheroids when cultured on polyamidoamine dendrimers modified with fructose. Because galactose is a ligand for the asialoglycoprotein receptor on the hepatocyte cytoplasmic membrane, it was chosen as another ligand for modification in order to maintain adhesion of spheroids for long periods. Simultaneous modification of dendrimers with fructose and galactose had a marked effect on the time length of spheroid adhesion. Suppression of apoptosis and necrosis was observed in hepatocyte spheroids cultured on a dendrimer modified with fructose and galactose (F/G dendrimer). Moreover, the hepatocyte spheroids cultured on the F/G dendrimer had higher activities of liver-specific functions, such as urea synthesis and albumin gene expression, than did those cultured on single-ligand-modified dendrimers. The expression of heat shock protein (HSP) genes was examined to evaluate the stress response of cells to scaffolds. The hepatocytes cultured on the F/G dendrimer had very low expression levels of both HSP60 and HSP70 mRNAs. Thus immobilization of mixed-ligand-modified dendrimers could generate a suitable surface for hepatocyte spheroid formation. These dendrimers could be a powerful tool for generating custom-made scaffolds for cells other than hepatocytes by selecting the ligands suitable for each cell type.
使用肝细胞类器官的混合人工肝
DOI：
--
发表时间：
2004
期刊：
Therapeutics & Engineering Vol.16, No.3
影响因子：
--
作者：
Y. Yoshihara;H. Sugawara;H. lto;K. Okada;and K. Masu;K.Nakazawa et al.
通讯作者：
K.Nakazawa et al.